15
Journal of Ayurveda Official publication of National Institute of Ayurveda, Jaipur, Rajasthan 117 JOA XIII-3 2019 ORIGINAL REASEARCH ARTICLE - LITERARY REVIEWS New insights of Ayurveda formulation Pushpadhanwa rasa as a palliative therapy to improve the quality of life in ovarian Cancer: A review *Dr. Manoj Kumar Dash, ** Dr. Namrata Joshi, ***Dr. D. N. S Gautam *Lecturer, Dept. of Rasashastra & Bhaishajya Kalpana, Govt. Ayurveda College Raipur, Chhattisgarh, **Associate Professor, ***Associate Professor, Dept. Of Rasashastra, Faculty of Ayurveda, IMS, BHU, Varanasi, ABSTRACT Introduction: Pushpadhanwa rasa is a formulation described under Aphrodisiac, has been used for centuries. It has been shown that minerals & herbal ingredients present in Pushpadhanwa rasa have been reported for their significant effects on different cell lines like HT-29, MMP-9, HeLa, HepG2, 5-FU, MCF-7, UWOV2, HCT-116 cells, relating to female reproductive organs. Aim of the study: In this study an attempt has been made to critical review the ovarian Cancer regression property of Herbo mineral preparation, Pushpadhanwa rasa (PDR) Materials & methods: Thirty one ingredients of herb-mineral-animal origin were searched from various authoritative texts and worldwide accepted scientific databases with regard to their use in female reproductive organs for cancer claims including the ovarian cause. Result: A total of 31 ingredients were evaluated for their anti-tumour activities in eight human cancer cell lines. Of these G. glabra, P.betel, C. sativa exhibited promising apoptosis activity, G. glabra exhibited anti proliferative & anti angiogenic, G. glabra, P. betel, T.Myrobalan, P. betel, exhibited anti oxidant, P. betel, Z.officinale exhibited anti metastatic, P.betel, Honey shows cytotoxic , C. sativa cell cycle arrest activity in many cancer cells. Bhasmas present in Pushpadhanwa rasa like Rasasindoora, Lauha bhasma, Abhraka Bhasma, Naga Bhasma, Manahshila are considered as biologically produced nano drugs. Conclusion: Above data shows that the formulation Pushpadhanwa Rasa possess strong potential in treatment of ovarian cancer. as biologically produced nano drugs. Conclusion: Above data shows Keywords : Pushpadhanwa Rasa; Anti- cancer ; Apoptosis; Cytotoxic; Nano particle; Antioxidant. Address of Correspondence: Dr. Manoj Kumar Dash Lecturer, Dept. of RS & BK Govt. Ayurveda College Raipur, Chhattisgarh. Email ID : [email protected] Contact No : 8817708049 How to Site the Article : Dash MK, Joshi N, Gautam DNS, New insights of Ayurveda formulation Pushpadhanwa rasa as a palliative therapy to improve the quality of life in ovarian Cancer: A review JOA XIII-3, 2019; 117 - 131 JOA journalofayurveda.in ISSN No: 2321-0435 that the formulation Pushpadhanwa Rasa possess strong potential in treatment of ovarian cancer. Randomized controlled trials of high quality with larger sample size and longer follow-up are needed to have significant evidence on the clinical use of Pushpadhanwa rasa on ovarian cancer.

ORIGINAL REASEARCH ARTICLE - LITERARY REVIEWSjournalofayurveda.in/uploads/article/JOA-DOYtEBtGOAQ2cxjF.pdf · Pushpadhanwa rasa like Rasasindoora, Lauha bhasma, Abhraka Bhasma, Naga

  • Upload
    others

  • View
    4

  • Download
    0

Embed Size (px)

Citation preview

Page 1: ORIGINAL REASEARCH ARTICLE - LITERARY REVIEWSjournalofayurveda.in/uploads/article/JOA-DOYtEBtGOAQ2cxjF.pdf · Pushpadhanwa rasa like Rasasindoora, Lauha bhasma, Abhraka Bhasma, Naga

Journal of Ayurveda Official publication of National Institute of Ayurveda, Jaipur, Rajasthan117

JO

A

XII

I-3

2

01

9

ORIGINAL REASEARCH ARTICLE - LITERARY REVIEWS

New insights of Ayurveda formulation Pushpadhanwa rasa as a palliative therapy to improve the quality of life in ovarian Cancer:

A review*Dr. Manoj Kumar Dash, ** Dr. Namrata Joshi, ***Dr. D. N. S Gautam

*Lecturer, Dept. of Rasashastra & Bhaishajya Kalpana, Govt. Ayurveda College Raipur, Chhattisgarh, **Associate Professor, ***Associate Professor, Dept. Of Rasashastra, Faculty of Ayurveda, IMS, BHU, Varanasi,

ABSTRACTIntroduction: Pushpadhanwa rasa is a formulation described under Aphrodisiac, has been used for centuries.

It has been shown that minerals & herbal ingredients present in Pushpadhanwa rasa have been reported for their significant effects on different cell lines like HT-29, MMP-9, HeLa, HepG2, 5-FU, MCF-7, UWOV2, HCT-116 cells, relating to female reproductive organs. Aim of the study: In this study an attempt has been made to critical review the ovarian Cancer regression property of Herbo mineral preparation, Pushpadhanwa rasa (PDR) Materials & methods: Thirty one ingredients of herb-mineral-animal origin were searched from various authoritative texts and worldwide accepted scientific databases with regard to their use in female reproductive organs for cancer claims including the ovarian cause. Result: A total of 31 ingredients were evaluated for their anti-tumour activities in eight human cancer cell lines. Of these G. glabra, P.betel, C. sativa exhibited promising apoptosis activity, G. glabra exhibited anti proliferative & anti angiogenic, G. glabra, P. betel, T.Myrobalan, P. betel, exhibited anti oxidant, P. betel, Z.officinale exhibited anti metastatic, P.betel, Honey shows cytotoxic , C. sativa cell cycle arrest activity in many cancer cells. Bhasmas present in Pushpadhanwa rasa like Rasasindoora, Lauha bhasma, Abhraka Bhasma, Naga Bhasma, Manahshila are considered as biologically produced nano drugs. Conclusion: Above data shows that the formulation Pushpadhanwa Rasa possess strong potential in treatment of ovarian cancer. as biologically produced nano drugs. Conclusion: Above data shows

Keywords : Pushpadhanwa Rasa; Anti- cancer ; Apoptosis; Cytotoxic; Nano particle; Antioxidant.

Address of Correspondence: Dr. Manoj Kumar DashLecturer, Dept. of RS & BKGovt. Ayurveda College Raipur, Chhattisgarh.

Email ID : [email protected]

Contact No : 8817708049

How to Site the Article : Dash MK, Joshi N, Gautam DNS, New insights of Ayurveda formulation Pushpadhanwa rasa as a palliative therapy to improve the quality of life in ovarian Cancer: A review JOA XIII-3, 2019; 117 - 131

JOAjournalofayurveda.in ISSN No:2321-0435

that the formulation Pushpadhanwa Rasa possess strong potential in treatment of ovarian cancer. Randomized controlled trials of high quality with larger sample size and longer follow-up are needed to have significant evidence on the clinical use of Pushpadhanwa rasa on ovarian cancer.

Page 2: ORIGINAL REASEARCH ARTICLE - LITERARY REVIEWSjournalofayurveda.in/uploads/article/JOA-DOYtEBtGOAQ2cxjF.pdf · Pushpadhanwa rasa like Rasasindoora, Lauha bhasma, Abhraka Bhasma, Naga

Journal of Ayurveda Official publication of National Institute of Ayurveda, Jaipur, Rajasthan118

Dash MK, Joshi N, Gautam DNS, New insights of Ayurveda formulation Pushpadhanwa rasa as a palliative therapy to improve the quality of life in ovarian Cancer: A review JOA XIII-3, 2019; 117 - 131

Introduction :Ovarian Cancer is the most lethal among all other gynecological Cancer amongst the women. Globally, nearly 2, 50,000 patients diagnosed with ovarian Cancer each year with more than 1, 40,000 Cancer specific death[1]. Only 20% of the ovarian cancer is diagnosed at first stage when the disease is limited to the ovary, 90% of the patient responds well with existing therapy. Stages divided in to 3 more categories, i.e., Stage 2 When the disease metastasized to both the ovaries and the pelvic region; stage 3, after the disease has metastasized to the intraperitoneal abdomen region or Stage 4 beyond the peritoneal cavity cure rate decrease substantially[2]. The century-old embryonal/gametogenesis theory of tumors proposed that tumors arise from germ cells and thus are in some way similar to the formation of gametes and fertilization[3][4]

Ovarian Cancer known to originates by imbalances in

hormone production and abnormal cell division in basic

epithelial cells, germ cells, mesenchymal tissue developing Cystic mass in ovary. Mutation and loss of TP 53 function is one of the most frequent genetic abnormalities in ovarian cancer and is observed in 60-80% of both sporadic and familial cases[5]. Ovarian Cancer patients present with dull abdominal pain, distention of abdomen from no apparent cause. In advanced stage patient developes ascites, palpable lower abdominal masses, gastro intenstinal symptoms and weight loss. Surgery is the primary treatment of choice, regardless of the histological type or stages of the Cancer. Total abdominal hysterectomy, with bilateral salpingo-oophorectomy and omentectomy, is the accepted standard treatment. Conservation of the uterus and contralateral ovary in young women desirous of bearing children may be considered only if the disease is limited to stage 1a ( Cancer limited to one ovary : ascites not present). In Stage 1 (when tumor confined to the ovary), Herbomineral formulations like Pushpadhanwa rasa may be helpful in improving the quality of life with existing anticancer drugs. In Ayurvedic concept,

Page 3: ORIGINAL REASEARCH ARTICLE - LITERARY REVIEWSjournalofayurveda.in/uploads/article/JOA-DOYtEBtGOAQ2cxjF.pdf · Pushpadhanwa rasa like Rasasindoora, Lauha bhasma, Abhraka Bhasma, Naga

Journal of Ayurveda Official publication of National Institute of Ayurveda, Jaipur, Rajasthan119

Dash MK, Joshi N, Gautam DNS, New insights of Ayurveda formulation Pushpadhanwa rasa as a palliative therapy to improve the quality of life in ovarian Cancer: A review, JOA XIII-3, 2019; 117 - 131

according to ‘Charaka’ and ‘Sushruta Samhitas’ cancer is described as inflammatory or non-inflammatory swelling and mentioned either as ‘Granthi’ (minor neoplasm) or ‘Arbuda‘ (major neoplasm)[6].

Shukra is the most excellent term to explain the thing that nourishes both the male and female reproductive tissues and its secretions. Its main function is Garbhotpadana – reproduction[7].

Gananatha sen has explained Physiology of Shukradhatu in female as Antah-Shukra and Bahi-Shukra[8]. Shukradhatu is formed Antah-Shukra and Bahi-Shukra. Antah-Shukra operate as in both sexes in Bala Varana Upachaya, growth of secondary sexual character, reproductive organ and individual sex spermatogenesis in male and growth of breast, oogenesis in woman. Bahi-Shukra acts as formation of sperm with spermatic fluid in male and secretions of bartholin, cervical glands during coitus in female. Artav or Raja is Updhatu of Rasadhatu.Vrishya are drugs that enhances “Shukra dhatu” in order to increase the reproductive capacity and health in both male and female[9]. Gynacecological problems like irregular menses, PCOD, unovulation, etc causes are due to improper functioning of of Shukra dhatu schematic detail about role of shukra dhatu in male & female reproductive organ is as below[10].

As oocytes contribute to reproduction[11] it will be of interest to assess the functional relevance of the acquisition of oocyte-like cells during tumor progression[12]. It has been reported that both parthenogenetic activation of oocyte in ovary[13] and preimplantation embryos have tumorigenicity potential[14] both cancer cells and oocytes display strong independence and survival ability.

Pushpadhanwa rasa, is a formulation described under Vrishya- Vajikaran (Aphrodisiac) Rogadhikar and has been used for centuries to treat various types of ovararian disorders[15]. It exhibits a number of health benefits in gynaecological disorders. It has also been clinically trialled and was found to be effective in the management of Polyctstic ovarian disorder (PCOD) - a clinical condition which may be included under Granthi[16].

In that study, it was found that the formulation is not only beffective in regression of the size of the cyst but also enhances the chances of conception in such patients[17]. Pushpadhnwa Rasa contains mainly five bhasmas viz. Rasa sindoor (Red sulphide of mercury); Abhraka bhasma (Incinerated mica); Lauha bhasma (Incinerated iron); Naga bhasma ( Incinertaed lead); Vanga bhasma (Incinerated tin) and five herbs namely Dhatura (Dhatura metal); Bhanga (Cannabis sativa); Madhuyashti (Glycyrrihiza glabra; Nagaavalli (Piper betel) and Shalamali (Salmalia malbarrica). Literally the word Aphrodisiac (Vrisya) denotes, the drugs, which potentiate sexual vigor or promote artava (ovarian parameters) or both. Aphrodisiac (Vrisya) drugs are those, which can enhance the oogenesis and sexual vitality in females. The Physiology of female sexual act and oogenesis are interpreted with aphrodisiac (Vrisya) Karma, in connection to this, their pathological aspects which is Vandhyatva (female infertility) are dealt in detail with their respective management. Loss of artava is the fore most characteristics of Vandhyatwa (infirtility), which is seen in Ovarian Cancer. As it includes multiple groups of symptoms, single drug formulations might cover only a fraction of the treatment, hence the search for a group of drugs, particularly, such a group of drugs which are having aphrodisiac (Vrishya) anti oxidant (Rasayana) and other multimodal pharmacological actions might be highly beneficial in changing the quality of life. Such formulations, being very beneficial in symptoms arising due to "Tridosha vitiation" (mainly vata) have been selected for the present study.

Materials & Methods:

In this review, Ayurvedic fundamentals and Modern counterpart that includes Vrishya (aphrodisiac) and Rasayana (anti oxident) effect; Rasapanchka (Rasa, Guna,Virya,Vipaka, Prabhav) of the formulation; Anti tumor mechanism like inducing apoptosis in tumor cells, anti-proliferation, arrest cell cycle, anti angiogenic, anti metastasis activity of herbal ingriedients and Nanodrug delivery system, in terms of Ayurvedic biological nano particals that may affect the progression of cancer, are

Page 4: ORIGINAL REASEARCH ARTICLE - LITERARY REVIEWSjournalofayurveda.in/uploads/article/JOA-DOYtEBtGOAQ2cxjF.pdf · Pushpadhanwa rasa like Rasasindoora, Lauha bhasma, Abhraka Bhasma, Naga

Journal of Ayurveda Official publication of National Institute of Ayurveda, Jaipur, Rajasthan120

Dash MK, Joshi N, Gautam DNS, New insights of Ayurveda formulation Pushpadhanwa rasa as a palliative therapy to improve the quality of life in ovarian Cancer: A review, JOA XIII-3, 2019; 117 - 131

critically analyzed. For this, Compilation and tabulation of properties of Pushpadhanwa rasa like aphrodisiac activity (Vrisya =which potentiate sexual vigor or promote artava or both), Garbhadosahara (regularizing the female hormones) activity, Rasayana (anti oxident) activity present in Jangama (animal), Audhbiha (Pertaining to plants), and Parthiva (Pertaining to Earth) dravyas in the pharmaceutical processing of Pushpadhanwa rasa has been complied from Charak samhita, Sushruta samhita and Rasashastriya litreture. Compilation & tabulation of Rasa Panchak (Pharmacodynamics) viz. Rasa (taste), Guna (quality), Virya (Bio potency) Vipaka (drug metabolism), action on doshas were also complied from relevant sources and tabulated. Referencs from various journals are collected for various mechanism involved for their anti tumor activity. The tabulated data is then analyzed critically.

Results:

Analysis of total 31 different ingredients of Jangama (animal), Audhbiha (Pertaining to plants), and Parthiva (Pertaining to Earth) origin present in the pharmaceutical processing of Pushpadhanwa rasa have been made with their role in accordance with Ayurvedic perspective and recent researches undergone.

Discussion:

Pushpadhanwa rasa can be an option as a palliative therapy for the patients suffering from Ovarian cancer. The formulation has been clinically tested for its role in regression of cyst size in patients of PCOD[17]. Not only this, it is also proved to be effective in psychological imbalances cognitive behavioural therapy suffering from PCOD[18]. Saddhatwamtaka Sharira needs a preparation for ovarian cancer which found to interfere with mitosis, DNA synthesis and the DNA repair system.

Formulations like Pushpadhanwa Rasa, which may involved mechanisms like apoptosis (form of programmed cell death), anti proliferative ( prevent or retard the spread of cells), cell cycle arrest (ensure proper division of the cell.), angiogenic inhibitor (substance that inhibits the growth of new blood vessels), anti metastasis

( substance that inhibits the spread from an initial or primary site to a different or secondary site within the host's body), anti oxidant (compounds that inhibit oxidation), cytotoxicity (quality of being toxic to cells), Cellular penetration , Catalytic (process of increasing the rate of a chemical reaction ), anti tumour , Inhibitors of Fatty acid synthesize activity, Inhibition of growth of tumour cell in ovarian and other reproductive carcinoma may be helpful in improving the quality of life in ovarian cancer patients as shown in table no 2.

Ingredients of Pushpadhanwa rasa may play their role by acting on following mechanism:

Apoptosis

Apoptotic potential effect of Glycyrrihiza glabra is by restricting enzymes connected to cancer progression and enhancing cancer suppressor enzymes or Caspase-independent pathways may be involved in the apoptotic mechanism in inhibition of Endometrial, Ovarian HT-29 cancer cells[19]. Glycyrrhizin also induced apoptosis in cervical cancer cells by exerting mitochondrial depolarization, glycyrrhizin induced cell cycle arrest in G0/G1 phase of cell cycle[20] .Piper betel apoptotic potential effect by transient increase of mitochondrial derived reactive oxygen species followed by persistent increase of nitric oxide[21]. Dhatura metel promotes apoptosis of cancerous cells by the phenolic agents or by Loss of mitochondrial membrane potential, DNA fragmentation and nuclear chromatin condensation, strongly support the ability to induce the cancer cell apoptosis though the mitochondrial pathway[22]. Cannabis sativa to persuade apoptosis by means of or devoid of cell cycle arrest via mitochondrial pathway. Cannabinidiol present in cannabis sativa reduces mitochondrial membrane potential, triggers the translocation of BID to the mitochondria, the release of cytochrome c to the cytosol, and, ultimately, the activation of the intrinsic apoptotic pathway in breast cancer cells[23]. Cannabinidiol in Cannabis sativa increased the generation of reactive oxygen species (ROS), and ROS inhibition blocked the induction of apoptosis[24].

Anti proliferation activity

Page 5: ORIGINAL REASEARCH ARTICLE - LITERARY REVIEWSjournalofayurveda.in/uploads/article/JOA-DOYtEBtGOAQ2cxjF.pdf · Pushpadhanwa rasa like Rasasindoora, Lauha bhasma, Abhraka Bhasma, Naga

Journal of Ayurveda Official publication of National Institute of Ayurveda, Jaipur, Rajasthan121

Dash MK, Joshi N, Gautam DNS, New insights of Ayurveda formulation Pushpadhanwa rasa as a palliative therapy to improve the quality of life in ovarian Cancer: A review, JOA XIII-3, 2019; 117 - 131

Anti proliferation activity of Glycyrrihiza glabra by activating JNK (c-Jun N-terminal kinase) signals in cancer cells. The (JNK) pathway is one of the major signaling cassettes of the mitogen-activated protein kinase (MAPK) signaling pathway functions in the control of a number of cellular processes, including proliferation, embryonic development and apoptosis[25]. Cell cycle study showed that glycyrrhizin induced cell cycle arrest in G0/G1 phase of cell cycle significantly reduced the cell viability of HeLa cells with a concomitant increase in nuclear condensation and DNA fragmentation[26]. Three myrobalan suppressed proliferation independent of p53 status in cancer cells HCT116 and in HCCSCs (Human colon cancer stem cells). Three myrobalan also induced p53-independent apoptosis in HCCSCs as indicated by elevated levels of cleaved PARP. Three myrobalan suppressed protein levels of c-Myc and cyclin D1, key proteins involved in proliferation, and induced apoptosis through elevation of Bax/Bcl-2 ratio. Furthermore, triphala inhibited HCCSCs colony formation[27]

Anti - angiogenesis

Angiogenesis study indicates that mast cell infiltration can enhance carcinogenesis and they have also long been known to drive angiogenesis and tumour growth[28] Glycyrrihza glabra has been studied for its Antiangiogenic potential[29]. Triphala exerts its biological effectiveness in human colon cancer cells while self-regulating their p53 status. p53 is considered the “the guardian of the genome” and it plays a critical role in tumor suppression by inducing growth arrest, apoptosis, and senescence, as well as by blocking angiogenesis[30]. Metastatic potential of Hydroxychavicol of Piper betel component effectively suppressed the adhesion of oral KB carcinoma cells to FN ( Fibro nectin) and collagen, suggesting that the anti-carcinogenic effects of piper betel may involve the differential stages of tumor invasion and metastasis[31] . Metastastic potential of zingiber officinalis showed that When ginger powder is dissolved in a solution containing ovarian cancer cultures, the mutant cells died[32].

Anti oxidant

Glycyrrihiza glabra exhibited maximum scavenging

activity against DPPH and nitric oxide free radicals, inhibited cancer cells HeLa and HepG2 considerably for its anti oxidant activity[33]. Maximum ferric dropping action and radical scavenging actions in opposition to DPPH, superoxide anion and nitric oxide radicals. Highest phenolic content implying the potential contribution of phenolics towards the antioxidant activities[34]. Immunostimulatory potential of bioactive fraction-10 from Dhatura stramonium that boosts the immune cells in breast cancer. Recent studies on three myrobalan showed significant decrease in MDA and increase in GSH & SOD in breast homogenate in breast cancer[35]. Piper betel Extracts exhibit cytotoxic effect on the breast cancer cell line MCF-7. The cytotoxic effect of piper betel extract was through the formation of electrophilic metabolites—quinone, quinone methide, and imine methide—via the oxidative metabolism of piper betel[36]

Cytotoxic activity

Cytotoxic activity of Three myrobalan (Triphala) effective in cell lines like human (MCF-7) and mouse (S115) breast cancer cell line, a human osteosarcoma cell line (HOS-1), a human prostate cancer cell line (PC-3) and a nontumorigenic, immortalized human prostate cell line (PNT1A) by inhibiting the rate of cell proliferation and inducing cell death in breast cancer[37]. Cell penetration effect of three myrobalan showed Nano size easily transported into cell nucleus and to specific target sites, Mild to moderated growth inhibitory activity on prostate cancer cell lines[38]. Salmalia Malbarica showed Inhibitors of Fatty acid synthesize activity preferentially repress cancer cell proliferation and induce cancer cell apoptosis without affecting nonmalignant fibroblasts[39]. The withonilides which are steroidal lactones present in the plant Dhatura metel have been reported to have a high anticancer activity against colorecto carcinoma (HCT-116) cell line[40]. Ginger extract considerably reduced the important expression of NF kappa B and TNF-alpha in rats. Ginger can act as an anti-cancer and anti-inflammatory agent through inactivating NFkappaB in the course of the suppression of the pro-inflammatory TNF-alpha[41]. Bee venom was correlated with an increase

Page 6: ORIGINAL REASEARCH ARTICLE - LITERARY REVIEWSjournalofayurveda.in/uploads/article/JOA-DOYtEBtGOAQ2cxjF.pdf · Pushpadhanwa rasa like Rasasindoora, Lauha bhasma, Abhraka Bhasma, Naga

Journal of Ayurveda Official publication of National Institute of Ayurveda, Jaipur, Rajasthan122

Dash MK, Joshi N, Gautam DNS, New insights of Ayurveda formulation Pushpadhanwa rasa as a palliative therapy to improve the quality of life in ovarian Cancer: A review, JOA XIII-3, 2019; 117 - 131

in the levels of various proliferative and antiapoptotic gene products, including Bcl-2, cIAP-2, XIAP, iNOS, COX-2, and cPLA2, which are regulated by NFκB. Their immune histochemical examination of the tumor part by H&E, and the increase antigens adjacent to PCNA along with Ki-67 discoloration information revealed to facilitate bee venom inhibited tumor cell enlargement in a dose-dependent approach in ovarian cancer.[42]

Biological Nano particles and Bhasma

Bhasma are claimed to be biologically produced nanoparticles, which are prescribed with several other medicines of Ayurveda[43]. Realger shows inhibition of growth and survival of tumour cell[44] preventing tumour growth by transdermal delivery along with suppression of B16 cell proliferation. Nano particles size (~20nm) of Rasa sindura, with material characterisation of Single phase α-Hgs with free of Hgo and organic molecules[45], Lauha bhasma of particle size Smaller than ~45 µm with sub seive size distribution range between 1.7 and 10.4 µm[46] , Vanga bhasma of particle size inbetween 12 to 53 nm showed higher levels of accumulation in tumours and high degree of penetration behaviour[47]. Naga bhasma a nano-crystalline (~60 nm) lead sulfide form (Pb2+) associated with the organic contents showed high degree of penetration behaviour[48]. Mercurial preparations aimed to restore the homeostasis thus reversing the proliferation of neoplastic cells in bone marrow[49]. Rasasindura increases the efficacy of the contents of the medicine pushpadhanwa rasa by its catalytic effect[50]. Abhrak Bhasma shows concentration dependent positive in vitro anticancer activity on prostate cancer cell lines. Anticancer activity of Abhrak Bhasma is in the order 100 Puti > 50 Puti > 20 Puti. Shataputi Abhrak Bhasma had maximum activity on prostate cancer cell lines almost equivalent to positive control drug adriamycin[51]. Nano technologies can increase the potency of traditional small molecules of drugs in addition to potentially providing a mechanism for treating previously incurable diseases like cancer[52].

Rasa panchaka and its role

Sweet taste (Madhura Rasa) is considered to be useful for the physiological tissue growth and regeneration of skeletal muscles (mamsa), adipose tissue (meda), and marrow and nervous tissue (majja). Bitter (Tikta rasa) phytonutrients (e.g., polyphenols, flavonoids, isoflavones, terpenes, and glucosinolates) appear to lower the risk of cancer by downregulation of glucose transporter 1 (GLUT1) and inhibition of glycolysis (via hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A), leading eventually to apoptosis. Several bitter compounds (chloroquine, quinidine, bitter melon extract, and cucurbitacins B and E) were described as inhibitors of tumour growth and proapoptotic agents in cancer cells[53]. Based on relevant references from classical tests and modern tests of dravyaguna, Sweet taste ( Madhura rasa) is seen in 15 dravyas, Astringent (Kashaya rasa) in 14 dravyas, Bitter taste ( Tikta ) in 12 dravyas, Katu ( Pungent) rasa in 9 dravyas, and Amla ( Sour) rasa in 5 dravyas as shown in table no 4. Among Guna (property), Rukshya (Dry) guna is found in 13 dravyas; Laghu (Light) in 10 dravyas; Guru (Heavy) in 8 dravyas; Snigdha (Unctous) in 7 dravyas; and Tikshna (Sharp) in 6 dravyas. Vipaka (transformation) has been found as Katu (Pungent) in 15 dravyas and Madhura (Sweet) in 14 dravyas. The Virya (Bio potency) of most of the dravyas is Ushna (Hot) that is 18 incomparison to 9 in Sheeta (Cold) Virya dravyas. Bitter taste (Tikta rasa), Katu ( Pungent) Vipaka, Ushna Virya and Laghu and Ruksha Gunas, so it acts as good Lekhana Dravya - a scraping agent on Apachit Meda. The drug Pushpadhawa rasa due to it Laghu guna, Katu ( Pungent) rasa and Ushna Virya acts as deepana and pachana and regulates the Agni. Katu, Tikta, Kasaya Rasa (bitter, pungent, and astringent taste), Ushna Virya (e.g., hot biopotency), and Katu Vipaka (catabolic active metabolites), and herbs with dry, coarse, light, and sharp biophysical properties have significantly greater possibilities of producing anticancer effects[54]. Vrisya activity is seen in 14 dravyas; Balya in 7 dravyas; Rasayana in 10 dravyas; Yoni Doshahara in 4 dravyas; and Putraprada in 2 dravyas as shown in table no 1 & 4. The formation of dhatu from rasa to sukra or artava is by the Sweet taste ( Madhura rasa)and vipaka,

Page 7: ORIGINAL REASEARCH ARTICLE - LITERARY REVIEWSjournalofayurveda.in/uploads/article/JOA-DOYtEBtGOAQ2cxjF.pdf · Pushpadhanwa rasa like Rasasindoora, Lauha bhasma, Abhraka Bhasma, Naga

Journal of Ayurveda Official publication of National Institute of Ayurveda, Jaipur, Rajasthan123

Dash MK, Joshi N, Gautam DNS, New insights of Ayurveda formulation Pushpadhanwa rasa as a palliative therapy to improve the quality of life in ovarian Cancer: A review, JOA XIII-3, 2019; 117 - 131

snigdha guna and sheeta Virya. These properties of the preparation of Pushpadhawa rasa act by Rasayana, Vrisya, Balya, Vayasthapaka, and Vata Samaka Karma. Various ingredients of Pushpadhanwa rasa are having Vata-Kapha Shamaka , Tridoshashamaka properties, which help to bring the affected Doshas in normal level. As a result, the symptoms like ovarian cancer may subside.

Estrogens (E2) are concerned in the etiology of ovarian cancer. Estrogens make production and anti-estrogens slow down ovarian cancer growth in vitro and in vivo. Estrogen deprivation and estrogen receptor (ER) blockade cause cell cycle arrest in susceptible ovarian cancers by increasing the cell cycle inhibitor, p27. A better understanding of Estrogen signaling in ovarian cancer will permit refinement of combinations of targeted therapy like Rasasindura, Abhraka Bhasma, lauha bhasma & Vanga bhasma with standard hormonal agents to improve treatment[55]. Abhraka Bhasma and Loha Bhasma improve the excellence of Rasa and Rakta Dhatu which in turn improve the rest of Dhatus and thus improve the general situation of the patient. The Bhasmas are biologically formed nanoparticles and are in use along with milk, butter, honey, or clarified butter thus; this makes these elements simply assimilable, eliminating their injurious effects and enhancing their biocompatibility. The size and shape of nano drugs is directly propoertional to the activity in desired disease.

The different nano size and thieir morphology as shown in table no III is direcly helped in increasing apoptosis[56].Evidences shows bhasmas present in Pushpadhanwa Rasa are nearer to nano crystalline materials can be effective in ovarian cancer as shown in table no III.

Treatment aspect of Ayurveda is divided into four categories as Prakritisthapani chikitsa (health maintenance), Rasayana chikitsa, (restoration of normal function), Roganashani chikitsa (disease cure) and Naishthiki chikitsa (spiritual approach)[57]. Pushpadhnwa Rasa may provide new avenues and paradigms for cancer by its biological active substances as well as targeting the involved mechanisms like apoptosis, anti proliferative, cell cycle arrest, angiogenic inhibitor, anti metastasis, anti oxidant, cytotoxicity, Cellular penetration , Catalytic, anti tumour , Inhibitors of Fatty acid synthesize activity, Inhibition of growth of tumour cell.

Conclusion

The therapeutic use of cancer chemotherapy in ovarian carcinoma has been restricted due to its non-specific or dose limiting cellular toxicity and development of multidrug resistance. In the direction of overcome this limitation various drug delivery system are being studied. Drugs mentioned in Pushpadhanwa rasa have multifarious pharmacological properties. From the above discusson it indicates that pushpadhanwa Ras may be used with a combination of anti cancerous drugs to enhance the quality of life in Ovarian Cancer.

Table no. I Rasapanchaka ( Pharmacodynamics) of Drugs used in the pharmaceutical processing of Puspadhanwa Rasa

S. No.

Ingredient Utility in preparing

Pushpadhanwa rasa

Pharmacodynamic / Pharmacological application

1 Madhu (Honey)

Anupana (vehicle) of pushpadhanwa

Ras

Madhura, Kasaya, Ruksha, Seeta , Madhura,Vata bardhak, Vrisya,

Virya bardhak, Antioxidan, Increase reproductive hormones, Fertility

enhancer

Page 8: ORIGINAL REASEARCH ARTICLE - LITERARY REVIEWSjournalofayurveda.in/uploads/article/JOA-DOYtEBtGOAQ2cxjF.pdf · Pushpadhanwa rasa like Rasasindoora, Lauha bhasma, Abhraka Bhasma, Naga

Journal of Ayurveda Official publication of National Institute of Ayurveda, Jaipur, Rajasthan124

2. Godugdha (Cow milk)

Samanya Shodhana

ofAbharaka,

Shodhana of Dhatur, Bhanga

Madhura, Guru, Snigdha, Abhisyandi, Madhura, Vata pitta nasak, Balya, Vrisya, Prajasthapana, Vandhya,

Rasayana, Vajikara, Rasabardhaka, Improving egg quality

3. Goghrita (Cow’s clarified butter)

Anupana ofPuspadhan

wa rasa,Amritikarana

of Lauha

Madhura, Visahara, Virya Bardhaka, Oja, Rasayana, Vrisya, General Debility

4. Gomutra (Cow urine)

Samanya Shodhana of Naga, Vanga and Louha

Katu ( Pungent),Tiksna,Usna, Katu ( Pungent),Pitta bardhak, Pacana,

Gulma, Sula, Vrishya, Rasayana, Utility in ovarian caner

5. Takra (Buttermilk)

Samanya Shodhana of

Naga,Vanga, and Louha, Abhraka

Madhura, Amla, Laghu, Usna, Kapha pitta nasak, Garbhavisa nasak, Vrisya,

Higher antioxidant and Radical Scavenging activity.

6. Til Sesamum indicum L. Taila

Samanya Shodhana of Naga,Vanga,

Louha, Abhraka

Madhura, Kasaya, Sukhma, Guru,Usna, Madhura vipaka , Pitta bardhaka,

Vrisya, Garbhasaya sodhaka, Bruhana, Yoni sula nasak, Balya, Anti oxidant

7. Kanji (Rice gruel)

Samanya Shodhana of Naga,Vanga,

Louha, Abhraka

Bhedi, Tiksna, Ushna, Pitta , bardhaka, Sula nasaka, Garbhasaya Sodhaka,

Vrisya, Enhancing LH secretion

8.Kulatha Kvatha Decoction of

Macrotyloma uniflorum (Lam.) Verdc.

Samanya Shodhana of

Naga, Vanga, Louha,Abhraka

Kasaya, Usna, Katu ( Pungent), Pitta vardhka, Sukrasmari nasak, Gulma

nasak, Vrisya, Anti oxidant effect

9.Haritaki

Terminalia chebula Retz.

Visesa shodhana of Louha, Trividha

paka of Louham

Pancharasa, Kasaya pradhana, Laghu Ruksha,Ushna, Vipaka Madhura,

Tridosa nasaka, Rasayana, Vrisya.

10

AmalakiPhyllanthus emblica L

Emblica officinalis Gaertn.

Visesa shodhana of Louha, Trvidha

louha paka, amruti karana of Louha.

Pancharasa, Guru, Ruksha, Sheeta, Madhura, Tridosa nasaka,Vrisya,Rasayana,

Garbhsayasotha26

Dash MK, Joshi N, Gautam DNS, New insights of Ayurveda formulation Pushpadhanwa rasa as a palliative therapy to improve the quality of life in ovarian Cancer: A review, JOA XIII-3, 2019; 117 - 131

Page 9: ORIGINAL REASEARCH ARTICLE - LITERARY REVIEWSjournalofayurveda.in/uploads/article/JOA-DOYtEBtGOAQ2cxjF.pdf · Pushpadhanwa rasa like Rasasindoora, Lauha bhasma, Abhraka Bhasma, Naga

Journal of Ayurveda Official publication of National Institute of Ayurveda, Jaipur, Rajasthan125

11

BibhitakiTerminalia bellirica (Gaertn.)

Roxb. Visesa shodhana of Louha, Abhraka

Kashaya, Ruksha, Laghu

12Nimbu

Citrus medica L.

Marana of vanga bhasma,Trividha

louha paka,Abhraka amruti karana

Ushna, Madhura, Kapha pitta nasaka, Balya, Amla, Laghu, Anusna, Madhura,Pitta bardhaka, Deepana,

Pachana, Pradara, Atyartava, Garbhasrava, Yoni vishodhana

13

Adraka

Zingiber officinale RoscoeShodhana of Manashila

Katu(Pungent),Tikshna,Rukshya,Guru, Ushna, Madhura, Kapha vata nasak,

Hridya,Vrisya, Increases the secretion of melatonin and serotonin phytochemicals

14

ArkaCalotropis procera (Aiton) Dryand.

Calotropis gigantea (L.) Dryand.Marana of

Abhraka bhasma

Katu (Pungent), tikta, Laghu, Ruksha, Tikshna, Sara, Ushna, Katu ( Pungent),

Vata bardhak, Balya, Rasayana, Increase the plasma secretion levels of

LH & FSH, Immuno modulator

15.Vata

Ficus indica Willd. Bhavana dravya of

Rasasindoora

Kasaya, Madhura, Rukshya, Seeta, Katu( Pungent), Kapha Pitta nasak,

Yonidoshanasaka,Vrisya Putradam, ,

Garbhakara, Vandhyanasaka , anti oxidant activity, Estrogenic activity

16. HaridraCurcuma longa L.

Visesa shodhan

Of Vanga

Katu ( Pungent),Tikta, Laghu, Rukshya, Ushna, Vipaka

Katu(Pungent),Kaphavatahara, Garbhastapaka, Garbhasaya raktata ,

Aphrodisiac, Menorrhagia

17.Chincha Tamarindus indica L.

Jarana dra-vya for Naga

& Vanga bhasma

Amla, Madhura, Laghu, Ruksha, Ushna, Katu( Pungent), Kaphavata nasak, Hridya, Swelling on the breast, Anti

oxidant

18. AswathaFicus religiosa L.

Jarana dravya for Naga & Vanga

bhasma

Kasya, Madhura, Ruksha, Guru, Seeta, Katu( Pungent), Kaphapittahara,Yoni

vishodhana, Rasayana, Vrishya, Balya.

19.Dhattura

Datura metel L.

Bhavana dravya of pushpadhan-

wa RasMadhura.kasaya, Tikta, Guru, Tikshna,

Balya, Rasayana

Dash MK, Joshi N, Gautam DNS, New insights of Ayurveda formulation Pushpadhanwa rasa as a palliative therapy to improve the quality of life in ovarian Cancer: A review, JOA XIII-3, 2019; 117 - 131

Page 10: ORIGINAL REASEARCH ARTICLE - LITERARY REVIEWSjournalofayurveda.in/uploads/article/JOA-DOYtEBtGOAQ2cxjF.pdf · Pushpadhanwa rasa like Rasasindoora, Lauha bhasma, Abhraka Bhasma, Naga

Journal of Ayurveda Official publication of National Institute of Ayurveda, Jaipur, Rajasthan126

20.Bhanga

Cannabis sativa L.

Bhavana dravya of pushpadhan-

wa Ras

Ruksha, Ushna, Katu ( Pungent), Kapha Vatahara. Garbhasaya sankocaka,

Vajikarana, Rasayana and Vajikrana, Garbhadhana , Vandhya

21.Yastimadhu

Glycyrrhiza glabra L.

Bhavana dravya of Pushpadhanwa

Ras

Madhura, Tikta, Guru, Snigdha, Seeta, Katu ( Pungent), Tridosa hara, Balya.

Rasayana

22.

SalmaliSalmalia malabarica (DC.) Schott

& Endl

Bhavana dravya of pushpadhanwa

Ras

Madhura, Kasaya, Pichilla, Guru, Seeta, Madhura, Pitta Vatahara, Brihana, Rasayana Balya, Rasayana, Vrisya,

Garbhasaya Chutihara.

23.Nagavalli Piper betle L.

Bhavana dravya of pushpadhanwa

Ras

Katu ( Pungent),Tikta, Kasaya, Laghu, Tikshna, Ushna, Katu ( Pungent), Vata hara, Srama nasaka, Vrisya,

Rasayana, Putraprad, Pragyabodhi, Dhatubardhaka

24. Rasa Sindoor (Red sulphide of Mercury)Preparation for Rasasindoora

Sadrasa, Snigdha, Guru, Ushna, Madhura,Tridosa nasaka,Vrisya, Balya,

Rasayana

25.Shuddha Gandhaka

(Purified/ processed Sulphur)Preparation for Rasasindoora

Madhura, Snigdha, Sara, Ushna, Katu ( Pungent), Tridosha Nasak, Rasayana,

Virya Vridhi.

26.Shuddha Manashila

(Purified/ processed Realgar)

Marana dravya of Naga bhasma

Tikta, Katu (Pungent), Ushna, Vatakapha nasak, Sarbasrestha

Rasayana.

27Shuddha Haritala (Purified/ processed

Orpiment)Marana dravya of

Vanga bhasma

Katu ( Pungent), Snigdha, Kasaya, Snigdha, Ushna, Katu ( Pungent), Kapha nasak, Virya Vridhikara

28. Naga bhasma(Calcined Lead)Preparation of

Puspadhanwa rasa

Tikta, Laghu, Sara, Rukshya, Ushna, Katu ( Pungent), Vata kapha nasak,Kamavala, Naga sata tulya

balam.

29.Vanga bhasma (Calcined Tin)

Prepa-ration of Pus-

padhanwa rasa

Tikshna, Ushna, Rukshya, Laghu, Sara, Ushna, Katu ( Pungent), Vata prakopa,

Balya, Vrisya, Prajakara.

30.Abhraka

Bhasma (Calcined Mica)

Prepa-ration of Push-

padhanwa rasa

Guru, Snigdha, Seeta, Madhura, Vata Kapha Nasak, Pragya bodhi, Khya nasak, Vrisya, Ayusya, Putraprada

Dash MK, Joshi N, Gautam DNS, New insights of Ayurveda formulation Pushpadhanwa rasa as a palliative therapy to improve the quality of life in ovarian Cancer: A review, JOA XIII-3, 2019; 117 - 131

Page 11: ORIGINAL REASEARCH ARTICLE - LITERARY REVIEWSjournalofayurveda.in/uploads/article/JOA-DOYtEBtGOAQ2cxjF.pdf · Pushpadhanwa rasa like Rasasindoora, Lauha bhasma, Abhraka Bhasma, Naga

Journal of Ayurveda Official publication of National Institute of Ayurveda, Jaipur, Rajasthan127

31. Louha bhasma (Calcined Iron)

Preparation of Puspadhanwa rasa

Guru, Rukshya, Seeta, Madhura Tridosa Nasak, Putraprada, Bala Kara, Vrisya,

Vayastambhna.

Dash MK, Joshi N, Gautam DNS, New insights of Ayurveda formulation Pushpadhanwa rasa as a palliative therapy to improve the quality of life in ovarian Cancer: A review ,JOA XIII-3, 2019; 117 - 131

Table no. II List of drugs present in Pushpadhanwa rasa with their mechanism of action on cancer cells

Name of the drug

Class Mechanism of action Cell line studied

Glycyrrhiza glabra

ApoptosisCaspase-independent pathways

Endometrial Carcinoma, Ovar-ian Carcinoma.

Anti-proliferation Activating JNK signals

Colon cancer Cells

Antiangiogenic Regulates metastasis-relating protein MMP-9 Colon cancer

Anti oxidant Scavenging activity against DPPH and nitric oxide

Piper betel

Apoptosis Release of cytochrome C from mito-chondria Chronic Myeloid leukaemia

Anti metastasis Inhibiting the growth Colon cancer cells

Anti oxidant Ferric reducing activity and Radical scavenging activities Breast cancer

Cyto toxic activity Extracts exhibit cytotoxic effect Breast Cancer

Anti oxidant Immunostimulatory potential of bio-active fraction-10 Breast Cancer

ApoptosisLoss of mitochondrial membrane potential, DNA fragmentation and nuclear chromatin condensation

Breast cancer

Cannabis sativa

Cell cycle arrest Via Mitochondrial pathway.Cervical cancer cells

ApoptosisReduces Mitochondrial membrane

potential.Breast Cancer

Triphala

(Three Myrobal-an)

CytotoxicInhibiting the rate of cell

proliferation.Breast cancer

Anti oxidant Significant decrease in MDA and increase in GSH & SOD Breast cancer

Cellular penetrationEasily transported into cell nucleus

and to specific target sites Prostrate Cancer

Page 12: ORIGINAL REASEARCH ARTICLE - LITERARY REVIEWSjournalofayurveda.in/uploads/article/JOA-DOYtEBtGOAQ2cxjF.pdf · Pushpadhanwa rasa like Rasasindoora, Lauha bhasma, Abhraka Bhasma, Naga

Journal of Ayurveda Official publication of National Institute of Ayurveda, Jaipur, Rajasthan128

Adraka

Zingib-er offici-nale Ros-

coe

Anti cancer Inactivating NF kappa B Liver Cancer

Anti metastasis Inhibition of NF-kB Ovarian cancer

Rasa Sindoor (Red sulphide of

Mercury)Catalytic Increase the efficacy of the contents of

the medicine. Cancer

Manahshila ( Realger)

Inhibition of growth Suppression of B16 cell Skin cancerAnti tumour effect Inhibiting DNA synthesis. Ovarian carcinoma cells

Honey Cyto toxic effectIncrease in the levels of various

proliferative and antiapoptotic genesOvarian cancer

Dash MK, Joshi N, Gautam DNS, New insights of Ayurveda formulation Pushpadhanwa rasa as a palliative therapy to improve the quality of life in ovarian Cancer: A review ,JOA XIII-3, 2019; 117 - 131

Table no. III List of Biological Nano Particle ~Bhasma present in Pushpadhanwa rasa

Table no. IV Rasa panchaka (Pharmacodynamics) of Pushpadhanwa Rasa

Name of the Nano bhasma Analysis reported Nano dimensional Partile sizeRasa Sindura

(Red sulphide of Mercury)Single phase α-Hgs , Free of Hgo and

organic moleculesNano particles size (~20nm)

Lauha Bhasma (Calcined Iron)Irregular shaped aggregates.

Nano dimensional particles (~28nm) Smaller than ~45 µm with sub seive size distribution range between 1.7

and 10.4 µmVanga Bhasma (Calcined Tin)

Agglomerised 12 to 53 nm

Naga Bhasma (Calcined Lead) Agglomerised ~60 nm

Rasa(Taste)

Number

Guna(Proper

ty)

Number

Vipaka(Final

transformation)

NumberVirya(Bio

potency)

Number

Dosaha prabhav

()Number

Madhura( Sweet )

15Rukshya

( Dry)13

Katu( Pungent)

15Ushna(Hot)

18Tridosha Shamak

6

Kasaya(Astringent)

14Laghu(Light)

10Madhura( Sweet )

14Sheeta(Cold) 9

Kapha Pitta

Shamak4

Tikta ( Bitter)

12Guru

(Heavy)8 - - - -

Kapha Vata

Shamak7

Katu ( Pungent)

9Snigdha(Unctuous )

7 - - - - -

Page 13: ORIGINAL REASEARCH ARTICLE - LITERARY REVIEWSjournalofayurveda.in/uploads/article/JOA-DOYtEBtGOAQ2cxjF.pdf · Pushpadhanwa rasa like Rasasindoora, Lauha bhasma, Abhraka Bhasma, Naga

Journal of Ayurveda Official publication of National Institute of Ayurveda, Jaipur, Rajasthan129

Dash MK, Joshi N, Gautam DNS, New insights of Ayurveda formulation Pushpadhanwa rasa as a palliative therapy to improve the quality of life in ovarian Cancer: A review, JOA XIII-3, 2019; 117 - 131

Amla(Sour)

5Tikshna(Sharp )

6 - - - - - -

References

1. Rao. MS., Galliford. CV., Low. PS., 2015. Principles in the design of ligand-targeted cancer therapeutics and imaging agents. Nat Rev Drug Discov 14: 203-219. https://www.ncbi.nlm.nih.gov/pubmed/25698644.

2. Robert. CB., Hennessy., Mills, GB., 2009. The biology of ovarian cancer. Nat Rev Cancer 415-428. https://www.ncbi.nlm.nih.gov/pubmed/19461667.

3. Bignold. L. P., Coghlan. B. L. & Jersmann. H. P. Hansemann, Boveri, 2006. chromosomes and the gametogenesis-related theories of tumours. Cell Biol. Int. 30, 640–644. https://onlinelibrary.wiley.com/doi/abs/10.1016/j.cellbi.2006.04.002.

4. Old. L. J., 2001. Cancer/testis (CT) antigens—a new link between gametogenesis and cancer. Cancer Immun. 1, 1. https://www.ncbi.nlm.nih.gov/pubmed/12747762.

5. Liu. et al., 2018. Abnormal gametogenesis induced by p53 deficiency promotes tumor progression and drug resistance. Cell Discovery.4:54. https:// www.nature.com/ articles/ s41421-018-0054-x.

6. Bhishagratha. KL., 1991. Sushruta samhita. Sushruta samhita, Choukhamba Orientalia, Varanasi.

7. Tripathi. B., 2011. Agnivesh’s Charak Samhita with Ayurved Dipika commentary of Chakrapani, Chikitsa sthana, 15/ 16- 17, published by Chaukhambha Bharati Academy Sanskrit, pp. 456.

8. Pournima. S., 2014. A Concept of Stri shukra: An Ayurvedic perspective, published by Int. J. Res. Ayurveda Pharm. 5(2), pp. 229-230. DOI: 10.7897/2277-4343.05245

9. Tripathi. B., 2011, Agnivesh’s Charak Samhita with Ayurved Dipika commentary of Chakrapani, Chikitsa sthana, 15/16 - 17. published by Chaukhambha Bharati Academy Sanskrit, page no 456.

10. Pournima. S., 2014 A concept of sTri-shukra: An Ayurvedic perspective. Int. J. Res. Ayurveda Pharm. 5(2):229-231. DOI: 10.7897/2277-4343.05245

11. Nicholas, C. R., Chavez, S. L., Baker, V. L. & Reijo Pera, R. A. 2009. Instructing an embryonic stem cell-derived oocyte fate: lessons from endogenous oogenesis. Endocr. Rev. 30, 264–283. doi: 10.1210/er.2008-0034.

12. Saitou, M. & Yamaji, M. 2012. Primordial germ cells in mice. Cold Spring Harb. Perspect. Biol. 4, a008375. doi: 10.1101/cshperspect.a008375

13. Stevens, L. C. 1976. Animal model of human disease: benign cystic and malignant ovarian teratoma. Am. J. Pathol. 85, 809–813. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2032664.

14. Old, L. J. 2001. Cancer/testis (CT) antigens—a new link between gametogenesis and cancer. Cancer Immun. 1, 1. https://www.ncbi.nlm.nih.gov/pubmed/12747762.

15. Sharma. S., 2009. Rasa Tarangini. Kashinath Shastri, editor, 11th ed. New Delhi: Motilal Banarasidas Publication; Chapter, Parishista. p.766

16. Anita G et al: Understanding PCOD An Ayurvedic Perspective. International Ayurvedic Medical Journal VOL 2 (3) 2018. 1035-1037. http://www.iamj.in/posts/images/upload/1035_1039.pdf

17. Dash Manoj et al, Evaluation of Pushpadhanwa Rasa a Generic Ayurvedic herbomineral formulation in ovarian syndrome- A pilot study, Journal of drug research in Ayurvedic science, 2011, Vol 32 ( 1) , 73-98. http://www.ccras.nic.in /sites /default /files/ viewpdf/ jras/ JRAS_Abstract_2011_Vol_32_Jan_to_June/7.pdf.

18. Dash et al, Effects Of Pushpadhanwa Rasa On Psychological Imbalances In Polycystic Ovarian Disease Patients And Its Management; Ayurpharm Int J Ayur Alli Sci. 2016, Vol. 5 (7 ) 90 – 97.

19. Hejazi.. II., et al. 2017. New insights into the antioxidant and apoptotic potential of Glycyrrhiza glabra L. during hydrogen peroxide mediated oxidative stress: An in vitro and in silico evaluation.Biomed Pharmacother.94: 265-279. https:// www.ncbi.nlm.nih.gov/ pubmed/28763750.

20. Farooqui. et al., 2018. Glycyrrhizin induces reactive oxygen species-dependent apoptosis and cell cycle arrest at G0/G1 in HPV18+ human cervical cancer HeLa cell line Biomedicine & Pharmacotherapy 97: 752–764. https:// www.ncbi.nlm.nih.gov/ pubmed/29107932

21. Chakraborty. JB et al., 2012. Hydroxychavicol, a Piper betle leaf component, induces apoptosis of CML cells through mitochondrial reactive oxygen species-dependent JNK and endothelial nitric oxide synthase activation and overrides imatinib resistance. Cancer Sci. 103(1):88-99. https://www.ncbi.nlm.nih.gov/pubmed/21943109.

22. Gini. C. Kuriakose1., 2014. In Vitro Cytotoxicity and Apoptosis Induction in Human Cancer Cells by Culture Extract of an Endophytic Fusarium solani Strain Isolated from Datura metel LKuriakose et al., Pharm Anal Acta , 5:4. DOI: 10.4172/2153-2435.1000293.

23. Sindiswa. T., 2016. Cannabidiol rather than Cannabis sativa extracts inhibit cell growth and induce apoptosis in cervical cancer cells, BMC Complement Altern Med. 16(1): 335. https://www.ncbi.nlm.nih.gov/pubmed/27586579.

24. Shrivastava. A., 2011. Cannabidiol Induces Programmed Cell Death in Breast Cancer Cells by Coordinating the Cross-talk between Apoptosis and Autophagy. Mol Cancer Ther; 10(7). https://www.ncbi.nlm.nih.gov/pubmed/21566064.

Page 14: ORIGINAL REASEARCH ARTICLE - LITERARY REVIEWSjournalofayurveda.in/uploads/article/JOA-DOYtEBtGOAQ2cxjF.pdf · Pushpadhanwa rasa like Rasasindoora, Lauha bhasma, Abhraka Bhasma, Naga

Journal of Ayurveda Official publication of National Institute of Ayurveda, Jaipur, Rajasthan130

25. Chen. CT. et al., 2018. Glabridin induces apoptosis and cell cycle arrest in oral cancer cells through the JNK1/2 signaling pathway. Environ Toxicol. 33(6):679-685. https://www.ncbi.nlm.nih.gov/pubmed/29663662.

26. Farooqui. et al. , 2018. Glycyrrhizin induces reactive oxygen species-dependent apoptosis and cell cycle arrest at G0/G1 in HPV18+ human cervical cancer HeLa cell line Biomedicine & Pharmacotherapy 97;752–764. https:// www.ncbi.nlm.nih.gov/ pubmed/29107932.

27. Vadde. et al., 2015. Triphala Extract Suppresses Proliferation and Induces Apoptosis in Human Colon Cancer Stem Cells via Suppressing c-Myc/Cyclin D1 and Elevation of Bax/Bcl-2 Ratio; BioMed Research International. http://dx.doi.org/10.1155/2015/649263

28. Khan. R. Et al, 2013. Glycyrrhizic acid suppresses the development of precancerous lesions via regulating the hyperproliferation, inflammation, angiogenesis and apoptosis in the colon of wistar rats, PLoS One. 8 (2). https:// journals.plos.org/ plosone/ article?id=10.1371/ journal.pone.0056020.

29. Hejazi. II. et al., 2017 . New insights into the antioxidant and apoptotic potential of Glycyrrhiza glabra L. during hydrogen peroxide mediated oxidative stress: An in vitro and in silico evaluation.Biomed Pharmacother. 94: 265-279. https:// www.ncbi.nlm.nih.gov/ pubmed/28763750.

30. Vadde. et al., 2015. Triphala Extract Suppresses Proliferation and Induces Apoptosis in Human Colon Cancer Stem Cells via Suppressing c-Myc/Cyclin D1 and Elevation of Bax/Bcl-2 Ratio; BioMed Research International. http://dx.doi.org/10.1155/2015/649263.

31. Chang. et al., 2002. Inducing the cell cycle arrest and apoptosis of oral KB carcinoma cells by hydroxychavicol: roles of glutathione and reactive oxygen species British Journal of Pharmacology. 135, 619 ± 630. https:// www.ncbi.nlm.nih.gov/ pmc/articles/ PMC1573166/.

32. Jennifer. Rhode. et al., 2007. Ginger inhibits cell growth and modulates angiogenic factors in ovarian cancer cells: BMC Complement Altern Med. 20; 7:44.https://www.ncbi.nlm.nih.gov/pubmed/18096028.

33. Anuthakoengkun. A., 2014. Inhibitory effect on nitric oxide production and free radical scavenging activity of Thai medicinal plants in osteoarthritic knee treatment. J Med Assoc Thai. 97 Suppl 8:S116-24. https://www.ncbi.nlm.nih.gov/pubmed/25518303.

34. Hiss. DC.et al., 2007. Combination of tunicamycin with anticancer drugs synergistically enhances their toxicity in multidrug-resistant human ovarian cystadenocarcinoma cells. Cancer Cell Int. 7(1):5. https://www.ncbi.nlm.nih.gov/pubmed/17439664.

35. Das. ND. et al., 2011. Terminalia chebula extract acts as a potential NF-.B inhibitor in human lymphoblastic T cells. Phytother Res. 2011; 25:927–34. https:// www.ncbi.nlm.nih.gov/ pubmed/21509843.

36. Chang. et al, 2002. Estimation of Total Flavonoid Content in Propolis by Two Complementary Colorimetric Methods: Journal of Food and Drug Analysis , 10(3):178-182. https://scialert.net/fulltextmobile/?doi=rjphyto.2016.67.74.

37. Saleem. A., 2002. Inhibition of cancer cell growth by crude extract and the phenolics of Terminalia chebula Retz. Fruit. J Ethnopharmacol. 81(3):327-36. https:// www.ncbi.nlm.nih.gov/ pubmed/12127233.

38. Kumar. Amit., 2014. A review of traditional anticancer nano-medicine: triphalaThe Pharma Innovation Journal.3(7): 60-66. http:// www.thepharmajournal.com/ vol3Issue7/ Issue_september_2014/ 19.1.pdf

39. Tundis. R., et al., 2014. In vitro cancer cell growth inhibition and antioxidant activity of Bombax ceiba (Bombacaceae) flower extracts. Nat Prod Commun. 9(5):691-4. https://www.ncbi.nlm.nih.gov/pubmed/25026723.

40. Nash. RJ. et al, 1993. Calystegines in Solanum and Datura species and the death’s-head hawk-moth (Acherontia atropus). Phytochem. 34: 1281–1283. doi:10.1016/0031-9422(91)80016-T.

41. Habib. SH., et al. 2008. Ginger extract (Zingiber officinale) has anti-cancer and anti-inflammatory effects on ethionine-induced hepatoma rats. Clinics (Sao Paulo). 63(6):807-13. https://www.ncbi.nlm.nih.gov/pubmed/19061005.

42. Alizadehnohi. M. et al. 2012. The synergistic cytotoxic effect of cisplatin and honey bee venom on human ovarian cancer cell line A2780cp , J Venom Res. https:// www.ncbi.nlm.nih.gov/ pmc/articles/PMC3522379/.

43. Pal.et al. Bhasma : The ancient Indian nanomedicine J Adv Pharm Technol Res. 2014 Jan-Mar; 5(1): 4–12. https://www.ncbi.nlm.nih.gov/pubmed/24696811.

44. Cheng. YX. et al., 2012. Realger induced apoptosis of cervical cancer cell line Shia via citochrome C release and caspase 3 and caspase – 9 activation Chinese journal of integrative medicine.18(5):359-65. http://en.cnki.com.cn/Journal_en/E-E058-ZZXJ-2013-08.htm.

45. Ramnan. N. et al, 2015. Investigating structural aspects to understand the putative/claimed non toxicity of the Hg based Ayurvedic drug Rasa sindura using XAFS; Journal of Synchrotone radiation.22(5);1233-1241. https:// www.ncbi.nlm.nih.gov/ pubmed/26289275.

46. Krishnamachary. B. et al, 2012. Scientific validation of the different purification steps involved in the preparation of an Indian ayurvedic medicine, Lauha bhasma. J Ethnopharmacol. 142:98–104. https://www.ncbi.nlm.nih.gov/pubmed/22561344.

47. Rudramma. H., 2010. Vanga Bhasma And Its XRD Analysis ; Ancient Science of Life, Vol. 29, No.4 ,Pp 24 -28.

48. Singh. SK.,et al. , 2010. Synthesis, characterization and histopathological study of a lead based Indian traditional drug: Naga Bhasma. Indian J. 72:24–30. doi: 10.4103/0250-474X.62232

Dash MK, Joshi N, Gautam DNS, New insights of Ayurveda formulation Pushpadhanwa rasa as a palliative therapy to improve the quality of life in ovarian Cancer: A review, JOA XIII-3, 2019; 117 - 131

Page 15: ORIGINAL REASEARCH ARTICLE - LITERARY REVIEWSjournalofayurveda.in/uploads/article/JOA-DOYtEBtGOAQ2cxjF.pdf · Pushpadhanwa rasa like Rasasindoora, Lauha bhasma, Abhraka Bhasma, Naga

Journal of Ayurveda Official publication of National Institute of Ayurveda, Jaipur, Rajasthan131

Dash MK, Joshi N, Gautam DNS, New insights of Ayurveda formulation Pushpadhanwa rasa as a palliative therapy to improve the quality of life in ovarian Cancer: A review, JOA XIII-3, 2019; 117 - 131

49. Ruhila. A.et al , 2018. Review of Anti-cancer Activity of Metals and Minerals. J Ayu Med Sci. 3(3):405-12.

50. Arunachalam. J., 2015. Researches on mercurial preparations: The prime requirement for their acceptance in medical world. AYU [serial online] 2015 [cited 2019 Jul 4];36:118-24. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4784119/.

51. Yogesh. L. et al. 2018. Effect of Puta on in vitro anticancer activity of Shataputi AbhrakBhasma on lung, leukemia and prostate cancer cell lines, JAIM. https://www.ncbi.nlm.nih.gov/pubmed/30391122.

52. Gopinath. et al., 2016. Herbo-Metallic Indian Nano-Medicine Abhrak Bhasma (MICA): A Periodical Review.RJPBCS 7(6) ,2373-2381. https:// pdfs.semanticscholar.org/ 3a24/ b36d8901a6f63fa7a5cb65db715c97ece9a0.pdf.

53. Singh. N., et al. 2014. Differential expression of bitter taste receptors in non-cancerous breast epithelial and breast cancer cells,”

Biochemical and Biophysical Research Communications, 446/ 2, 499– 503. https://www.ncbi.nlm.nih.gov/pubmed/24613843

54. Singh. RH., 2002. An assessment of the ayurvedic concept of cancer and a new paradigm of anticancer treatment in Ayurveda. J Altern Complement Med.8(5):609-14. https://www.ncbi.nlm.nih.gov/pubmed/12470442.

55. Arlene. et al., 2013. New insights on the role of hormonal therapy in ovarian cancer Fiona Steroids. Author manuscript; available in PMC 2015 Aug 27. Published in final edited form as: Steroids. 78(6): 530–537. https:// www.ncbi.nlm.nih.gov/ pmc/ articles/ PMC4551472/.

56. Ruhila. A., et al. 2018. Review of Anti-cancer Activity of Metals and Minerals. J Ayu Med Sci. 3(3):405-12. http://www.jayumedsci.com/article/2018/3/3/105530 jams 2018320.

57. Thatte. U., et al. 1991. Ayurveda, the natural alternative. Sci Today. 2001:12–8.

lkjka'k%

ifjp;:- iq"i/kUok jl ,d vk;qosZfnd jl©"kf/k gS ftldk mi;¨x okthdj æO;¨a ds vUrxZr lfn;¨a ls fd;k tkrk jgk gSA iq"i/kUok jl

esa e©twn [kfut vkSj gcZy æO; fofÒé dSalj lsy ykbu¨a t¨ fd efgyk Átuu vax¨a ls lacaf/kr d¨f'kdk,a tSls HT-29] MMP-9] Hela] HepG2, 5-FU, MCF-7, UVOV2, HCT-116 bR;kfn ij ÁÒkoh :i ls dk;Zdkjh ik, x, gSaA

v/;;u dk mÌs';:- bl v/;;u esa gjc¨feusjy ;¨x] iq"i/kUok jl ds fMEcxzafFk dSalj fjxzs'ku dh leh{kk djus dk Á;kl fd;k x;k gSA

lkexzh vkSj fof/k;k¡:- jl©"kf/k fuekZ.k esa tM+h cwVh-[kfut-i'kq mRifÙk dh bdrhl lkefxz;¨a d¨ fofÒé vkf/kdkfjd xzaFk¨a vkSj nqfu;k Òj

esa Lohdkj fd, x, oSKkfud MsVkcsl ls fMEcxzafFk ds dkj.k lfgr dSalj ds fujkdj.k ds fy, efgyk Átuu vax¨a esa muds mi;¨x ds

laca/k esa [k¨tk x;k gSA

ifj.kke:- vkB ekuo dSalj lsy ykbu¨a esa muds ,aVh-VÓwej xfrfof/k;¨a ds fy, dqy 31 tM+h cwVh-[kfut-i'kq mRifÙk dk ewY;kadu fd;k

x;k gS A buesa ls ;f"Ve/kq] rkEcwy] Òkax vk'kktud ,i¨IV¨fll xfrfof/k d¨ Ánf'kZr djrk gs] tcfd ;f"Ve/kq esa ,aVh Á¨fyQsjsfVo ,aM

,aVh ,aft;¨tsfud] ;f"Ve/kq] rkEcwy] f=Qyk esa ,aVh vkWDlhMsaV ,fDVfoVh ik;h xà A vkæd dà dSalj d¨f'kdkvksa esa ,aVh esVkLVSfVd]

rkEcwy ,oa 'kgn lkbV¨V‚fDld tcfd Òkax lsy lkbfdy vjsLV xfrfof/k Ánf'kZr djrk gsSs A iq"i/kUok jl esa e©twn ÒLe tSls jlflanwj]

y©g ÒLe] vÒzd ÒLe] ukx ÒLe] eu%f'kyk d¨ tSfod :i ls mRikfnr uSu¨ Mªx ekuk tkrk gSA

fu"d"kZ:- mij¨ä vkadM+¨a ls irk pyrk gS fd vks"kf/k dSalj ds mipkj esa iq"i/kUok jl dh Ácy laÒkouk gSA cM+s uewus ds vkdkj ds lkFk

mPp xq.koÙkk js.MksekbTM daVª¨YM ijh{k.k¨a vkSj fMEcxzafFk ds dSalj ij iq"i/kUok jl ds uSnkfud mi;¨x ij egRoiw.kZ Áek.k g¨us ds fy,

yacs le; rd vuqorÊ dkjZokà dh vko';drk gSA