Bhushan Patwardhan

Ayurveda and traditional Chinese medicine: a comparative overview.

Ayurveda, the traditional Indian medicine (TIM) and traditional Chinese medicine (TCM) remain the most ancient yet living traditions. There has been increased global interest in traditional medicine. Efforts to monitor and regulate herbal drugs and traditional medicine are underway. China has been successful in promoting its therapies with more research and science-based approach, while Ayurveda still needs more extensive scientific research and evidence base. This review gives an overview of basic principles and commonalities of TIM and TCM and discusses key determinants of success, which these great traditions need to address to compete in global markets.

Studies on the immunomodulatory effects of Ashwagandha

The immunomodulatory activity of an Indian Ayurvedic medicinal preparation, Ashwagandna (Withania somnifera (L. Dunal)) was studied in mice with myelosuppression induced by one or more of the following three compounds: cyclophosphamide, azathioprin, or prednisolone. The assessment of immunomodulatory activity was carried out by hematological and serological tests. A significant modulation of immune reactivity was observed in all the three animal models used. Ashwagandha prevented myelosuppression in mice treated with all three immunosuppressive drugs tested. A significant increase in hemoglobin concentration (P < 0.01), red blood cell count (P < 0.01), white blood cell count (P < 0.05), platelet count (P < 0.01), and body weight (P < 0.05) was observed in Ashwagandha-treated mice as compared with untreated (control) mice. We also report an immunostimulatory activity: treatment with Ashwagandha was accompanied by significant increases in hemolytic antibody responses towards human erythrocytes.

Traditional medicine-inspired approaches to drug discovery: can Ayurveda show the way forward?

Drug discovery strategies based on natural products and traditional medicines are re-emerging as attractive options. We suggest that drug discovery and development need not always be confined to new molecular entities. Rationally designed, carefully standardized, synergistic traditional herbal formulations and botanical drug products with robust scientific evidence can also be alternatives. A reverse pharmacology approach, inspired by traditional medicine and Ayurveda, can offer a smart strategy for new drug candidates to facilitate discovery process and also for the development of rational synergistic botanical formulations.

Treatment of osteoarthritis with a herbomineral formulation: a double-blind, placebo-controlled, cross-over study

The clinical efficacy of a herbomineral formulation containing roots of Withania somnifera, the stem of Boswellia serrata, rhizomes of Curcuma longa and a zinc complex (Articulin-F), was evaluated in a randomized, double-blind, placebo controlled, cross-over study in patients with osteoarthritis. After a one-month single blind run-in period, 42 patients with osteoarthritis were randomly allocated to receive either a drug treatment or a matching placebo for a period of three months. After a 15-day wash-out period the patients were transferred to the other treatment for a further period of three months. Clinical efficacy was evaluated every fortnight on the basis of severity of pain, morning stiffness, Ritchie articular index, joint score, disability score and grip strength. Other parameters like erythrocyte sedimentation rate and radiological examination were carried out on a monthly basis. Treatment with the herbomineral formulation produced a significant drop in severity of pain (P less than 0.001) and disability score (P less than 0.05). Radiological assessment, however, did not show any significant changes in both the groups. Side effects observed with this formulation did not necessitate withdrawal of treatment.

Studies on immunomodulatory activity of Withania somnifera (Ashwagandha) extracts in experimental immune inflammation

The immunomodulatory activities of an Indian Ayurvedic medicinal preparation, i.e. extracts from Ashwagandha, Withania somnifera (L.) Dunal (Solanaceae), namely WST and WS2, were studied in mice for immune inflammation: active paw anaphylaxis and delayed type hypersensitivity (DTH). Immunomodulatory effect was assessed in If IgE-mediated anaphylaxis as reduction of ovalbumin-induced paw edema, in animals treated with WS2 at doses of 150 and 300 mg/kg, and the results were compared with the standard drug disodium chromoglycate. In the DTH model, the modulatory effect was assessed as potentiation or suppression of the reaction, revealing an increase or decrease in mean foot pad thickness, respectively. Potentiation of the DTH reaction was observed in animals treated with cyclophosphamide at a dose of 20 mg/kg, WST at a dose of 1000 mg/kg and WS2 at a dose of 300 mg/kg. On the other hand, cyclophosphamide-induced potentiation of DTH reaction was suppressed in animals treated with WST and WS2. A significant increase in white blood cell counts and platelet counts was observed in animals treated with WST. A protective effect in cyclophosphamide-induced myelosuppression was observed in animals treated with WST and WS2, revealing a significant increase in white blood cell counts and platelet counts. Cyclophosphamide-induced immunosuppression was counteracted by treatment with WS2, revealing significant increase in hemagglutinating antibody responses and hemolytic antibody responses towards sheep red blood cells.

Botanical immunodrugs: scope and opportunities

Abstract Modulation of the immune system can be addressed through a variety of specific and non-specific approaches. Many agents of synthetic and natural origin have stimulatory, suppressive or regulatory activity. There is growing evidence that drugs or biological agents capable of modulating single pathways or targets are of limited value as immune-related therapies. Systems biology approaches are now gaining more interest compared with monovalent approaches, which can be of limited benefits with complications. This has stimulated interest in the use of ‘cocktails’ of immunodrugs to restore immunostasis. Botanicals are chemically complex and diverse and could therefore provide appropriate combinations of synergistic moieties useful in drug discovery. Here, the importance of traditional medicine in natural product drug discovery related to immunodrugs is reviewed.

A 32-week randomized, placebo-controlled clinical evaluation of RA-11, an Ayurvedic drug, on osteoarthritis of the knees.

Background:The ancient Indian (Asian) Ayurvedic medicinal system uses herbomineral drugs to treat arthritis. Despite centuries of use, very few have been tested by drug trials. RA-11 (ARTREX, MENDAR), a standardized multiplant Ayurvedic drug (Withania somnifera, Boswellia serrata, Zingiber officinale, and Curcuma longa) is currently used to treat arthritis. Objective:The objective of this study was to evaluate the efficacy and safety of RA-11 in patients with symptomatic osteoarthritis (OA) of the knees. Methods:A total of 358 patients with chronic knee pain were screened free-of-cost in “arthritis camps” in an Indian metropolis. Ninety patients with primary OA of the knees (ACR classification; Arthritis Rheum 1986;29:1039–1049) were found eligible (postanalgesic washout pain visual analog score [VAS] ≥40 mm in either or both knees on body weight-bearing activities) to enroll into a randomized, double-blind, placebo-controlled, parallel efficacy, single-center, 32-week drug trial (80% power to detect 25% difference, P = 0.05, 2-sided). Concurrent analgesics/nonsteroidal antiinflammatory drugs and steroids in any form were not allowed. Lifestyle and/or dietary restrictions, as per routine Ayurveda practices, were not imposed. Pain VAS (maximum pain in each knee recorded by the patient during the preceding 48 hours) and modified WOMAC (Western Ontario McMaster University OA Index, Likert scale, version 3.0) were the primary efficacy variables. The WOMAC section on “physical function difficulty” was modified for Indian use and validated before the trial. Routine laboratory testing was primarily done to monitor drug safety. At baseline, the groups (active = 45, placebo = 45) were well matched for several measures (mean pain VAS: active = 6.17; placebo = 6.5). Results:1) Efficacy: Compared with placebo, the mean reduction in pain VAS at week 16 (active = 2.7, placebo = 1.3) and week 32 (active = 2.8, placebo = 1.8) in the active group was significantly (P <0.05, analysis of variance [ANOVA]) better. Similarly, the improvement in the WOMAC scores at week 16 and week 32 were also significantly superior (P <0.01, ANOVA) in the active group. 2) Safety: Both the groups reported mild adverse events (AE) without any significant difference. 3) Withdrawals: Twenty-eight patients were discontinued. None reported drug-related toxicity. The majority failed follow up/compliance. No differences were observed between the groups. Conclusion:This controlled drug trial demonstrates the potential efficacy and safety of RA- 11 in the symptomatic treatment of OA knees over 32 weeks of therapy.

Immunomodulatory activity of Asparagus racemosus on systemic Th1/Th2 immunity: Implications for immunoadjuvant potential

ETHNOPHARMACOLOGICAL RELEVANCE Roots of Asparagus racemosus Willd (Shatavari in vernacular) are widely used in Ayurveda as Rasayana for immunostimulation, galactogogue as also in treatment of conditions like ulcers and cancer. Various studies have indicated immunomodulatory properties of Shatavari root extracts and formulations. AIM OF THE STUDY To study the effect of standardized Asparagus racemosus root aqueous extract (ARE) on systemic Th1/Th2 immunity of SRBC sensitized animals. MATERIALS AND METHODS We used HPTLC to quantify steroidal saponins (Shatavarin IV, Immunoside) and flow cytometry to study effects of ARE on Th1/Th2 immunity. SRBC specific antibody titres and DTH responses were also monitored as markers of Th2 and Th1 responses, respectively. We also studied lymphocyte proliferation. Cyclosporin, cyclophosphamide and levamisole were used as controls. RESULTS Treatment with ARE (100mg/(kg b.w.p.o.)) resulted in significant increase of CD3(+) and CD4/CD8(+) percentages suggesting its effect on T cell activation. ARE treated animals showed significant up-regulation of Th1 (IL-2, IFN-g) and Th2 (IL-4) cytokines suggesting its mixed Th1/Th2 adjuvant activity. Consistent to this, ARE also showed higher antibody titres and DTH responses. ARE, in combination with LPS, Con A or SRBC, produced a significant proliferation suggesting effect on activated lymphocytes. CONCLUSION The study suggests mixed Th1/Th2 activity of ARE supports its immunoadjuvant potential.

HLA and disease.

Association of HLA and diseases is well known. Several population studies are available suggesting evidence of association of HLAs in more than 40 diseases. HLA found across various populations vary widely. Some of the reasons attributed for such variation are occurrence of social stratification based on geography, language and religion, consequences of founder effect, racial admixture or selection pressure due to environmental factors. Hence certain HLA alleles that are predominantly associated with disease susceptibility or resistance in one population may or may not show any association in other populations for the same disease. Despite of these limitations, HLA associations are widely studied across the populations worldwide and are found to be important in prediction of disease susceptibility, resistance and of evolutionary maintenance of genetic diversity. This review consolidates the HLA data on some prominent autoimmune and infectious diseases among various ethnic groups and attempts to pinpoint differences in Indian and other population.

The assessment of osteoporosis risk factors in Iranian women compared with Indian women

BackgroundOsteoporosis is an important public health problem in older adults. It is more common in postmenopausal women and not only gives rise to morbidity but also markedly diminishes the quality of life in this population. There is lack of information about the risk factor of osteoporosis in developing countries. In this study we aimed to assess the risk factors for osteoporosis in postmenopausal women from selected BMD centers of two developing Asian countries (Iran and India).MethodsThis study is a multicenter interview-based study conducted in selected hospitals and health centers from urban areas in Iran and India. The case group included postmenopausal osteoporotic women who were identified as patients with bone density higher than 2.5 SD below average of young normal bone density (in L1–L4) spine region interest and/or total femoral region) by using DEXA method. The controls were chosen from postmenopausal women with normal bone density (in L1–L4 spine and total femoral regions using DEXA method) matching in age groups was strategy of choice.The sample sizes included from Iran a total of 363 subjects (178 osteoporotic and 185 normal) and from India a total of 354 subjects (203 osteoporotic and 151 normal).ResultsThe significant (p < 0.05) risk factors in present study population with their Odds Ratios (in parenthesis, respectively in Iran and India) were as follow:Lower education defined as less than class 12 or nil college (2.1) (2.7), duration of menopause greater than 5 years: (2.2) (1.4), Menarche age (after 14 years): (1.9) (1.6), Menopause age (before 45 years): (1.1) (2), Parity more than 3: (1.1) (1), Bone and joint problem (2.3) (2.2).Calcium supplementation (0.6) and HRT (0.4) were shown as protective factors and steroid therapy (3.3) was found as a risk factor in Iran. Calcium supplementation more than 1 year (0.3) was shown as a protective factor in India.Pure vegetarianism: (2.2) and Red meat consumption more than 4 times per week (1.4) was shown as a risk factor in Indian and Iranian subjects respectively.Regular consumption of Soya (0.3), almond (0.5), fish (0.5), fruits (0.4) and milk tea 4 cups per day and more (0.4) appeared to be significant protective factors in India. Regular consumption of cheese (0.5), milk (0.5), chicken (0.4), egg (0.6), fruit (0.4), tea 7 cups per day and more (0.3) were found to be significant protective factors in Iran. Exercises were shown as protective factor in Iran (0.4) and India (0.4).There were no significant differences in association of risk factors and osteoporosis between Iranian and Indian subjects.ConclusionOsteoporosis in Iranian and Indian subjects also appears to be associated with several known risk factors that well described in the literature. There were no significant differences in association of risk factors and osteoporosis between Iranian and Indian subjects. It was shown a protective role of certain nutritional dietary components and also exercises in both populations and can be exploited in preventive educational strategies on osteoporosis in these populations.