ABSTRACT
Plants have been the main source of therapeutic agents in world’s most ancient system of medicine, the Ayurveda. Nimb (also known as Margosa tree) is one of the most commonly used plants in Ayurveda for the management of a large number of ailments. It is a member of the Meliaceae family, found commonly in India, Africa and America. Nimb has been used exclusively by mankind to treat various diseases since even before the availability of manuscripts that recorded the beginning of history. Nimb is well described in Charak Samhita, Sushrut Samhita, Ashtang Hridayam, Chikitsa grantha and Nighantus. It is having Laghu guna, Tikta kashaya rasa, Sheeta virya and Katu vipaka, due to which it has been considered as Kapha-pitta shamaka. Acharya Bhav Mishra considers it Tridosh Shamak. It is traditionally used in the treatment of various ailment i.e., Krimi, Kushtha, Jwara, Kandu, Shopha and many more. All the parts of the plant have been used in the preparation of therapeutic formulations. Nimb contains various bioactive compounds like Nimbinin and Nimbidin, due to which it shows antibiotic, antiulcer, anti-inflammatory, antihelmenthic, antifungal, diuretic, antihistaminic, nematicidal and spermicidal properties and other biological activities. Present paper is an effort to validate pharmacological properties of Nimb described in Ayurveda through reverse pharmacology.
ABSTRACT
BACKGROUND/AIMS: Hepatic steatosis is caused by an imbalance between free fatty acids (FFAs) uptake, utilization, storage, and disposal. Understanding the molecular mechanisms involved in FFAs accumulation and its modulation could drive the development of potential therapies for Nonalcoholic fatty liver disease. The aim of the current study was to explore the effects of picroside II, a phytoactive found in Picrorhiza kurroa, on fatty acid accumulation vis-à-vis silibinin, a known hepatoprotective phytoactive from Silybum marianum. METHODS: HepG2 cells were loaded with FFAs (oleic acid:palmitic acid/2:1) for 20 hours to mimic hepatic steatosis. The FFAs concentration achieving maximum fat accumulation and minimal cytotoxicity (500 μM) was standardized. HepG2 cells were exposed to the standardized FFAs concentration with and without picroside II pretreatment. RESULTS: Picroside II pretreatment inhibited FFAs-induced lipid accumulation by attenuating the expression of fatty acid transport protein 5, sterol regulatory element binding protein 1 and stearoyl CoA desaturase. Preatreatment with picroside II was also found to decrease the expression of forkhead box protein O1 and phosphoenolpyruvate carboxykinase. CONCLUSIONS: These findings suggest that picroside II effectively attenuated fatty acid accumulation by decreasing FFAs uptake and lipogenesis. Picroside II also decreased the expression of gluconeogenic genes.
Subject(s)
Fatty Acid Transport Proteins , Fatty Acids, Nonesterified , Hep G2 Cells , Lipogenesis , Milk Thistle , Non-alcoholic Fatty Liver Disease , Phosphoenolpyruvate , Picrorhiza , Stearoyl-CoA Desaturase , Sterol Regulatory Element Binding Protein 1ABSTRACT
The elaboration of the mechanism and pharmacodynamic substance are the main obstacles to the modernization of Chinese medicine.The rich ingredient of Chinese medicine is almost attention,with a research strategy of forward pharmacology.This strategy often neglects the study of trace components of Chinese medicine.Synthetic lethality,a extremely complex gene interactions,is to magnify the effects of the co-regulation of biological effects (＞ 1 000 times).The theory of synthetic lethality has achieved good results in the development of anti-tumor drugs,including the discovery of PARP inhibitors,the clinical use of chemotherapy drug addition and attenuation combination.In view of this,this research model may be used to elucidate trace effective substance.Based on the reverse thinking of "targetcomponent-effect"and clear synergistic targets,the mechanism of traces and weak-potency substance of traditional Chinese medicine was studied,and the synergistic combination of potential was found.
ABSTRACT
Background: AmrutBhallatak (ABFN02), a ‘rasayana’ drug from Ayurveda is indicated in degenerative diseases and arthritis. Objective: To evaluate safety and effi cacy of ABFN02 in osteoarthritis (OA) and compare it with Glucosamine sulphate (GS) Materials and Methods: This was a randomized open comparative study. Ambulant OPD patients of OA knees (n = 112) were enrolled for 24 weeks. Tablets (750mg each) of GS and ABFN02 were matched. Three groups of patients: (A) GS, one tablet × twice/day × 24 weeks. (B) ABFN02, incremental pulse dosage (one tablet x twice/day × two weeks, two tablets × twice/day × two weeks, three tablets × twice/day × two weeks), two such cycles of drug and non-drug phases alternately for six weeks each (C) ABFN02 continuous dosage akin to GS. Pain visual analogue score (Pain-VAS) and Western Ontario and Mc-Master University Osteoarthritis Index (WOMAC) were the primary outcome measures. Secondary outcome measures were Health assessment questionnaire (HAQ), paracetamol consumption, 50 feet walking, physician and patient global assessment, knee stiffness, knee status, urinary CTX II, serum TNFa-SRI, SRII and MRI knee in randomly selected patients. Results: ABFNO2 and GS demonstrated, adherence to treatment 87.75% and 74.3%, reduction in Pain-VAS at rest 61.05% and 57.1%, reduction in pain-VAS on activity 57.4% and 59.8%, WOMAC score drop 62.8% and 59.1% respectively. Secondary outcome measures were comparable in all groups. Safety measures were also comparable. No serious adverse events reported. However, asymptomatic reversible rise in liver enzymes was noted in the ABFNO2 group. Conclusions: ABFN02 has signifi cant activity in OA; the formulation needs further investigation.
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Dr. Ashok D.B. Vaidya, the stalwart in the fields of Experimental Pharmacology, Clinical Pharmacology, and Reverse Pharmacology turns 75 on Nov, 27, 2011. A former Clinical Research Head of CIBA Geigy Research Centre, his name has been synonymous with the concept of the Golden Triangle for resurgence of Ayurveda and its reinterpretation in modern scientific terms. At a time when most fields are populated by intellectual dwarfs and unethical operators, he stands like a giant—a scientist, a philosopher, and an ardent fighter for ethical values. In this free-wheeling interview with Ravindra R.Pandharinath, he discusses the milestones in his life, his inspirations, and dreams for the confluence of modern science, modern medicine, and Ayurveda as the new health care model for the 21st century
ABSTRACT
This paper reviews the pharmacology of Indian medicinal plants, starting with the historical background of European work on the subject beginning as early as the 17th century, and tracing its history through the work of Sen and Bose in the 1930’s, and Vakhil’s historic 1949 paper on Sarpaghanda. The often crucial role of patient feedback in early discoveries is highlighted, as is the time lag between proof of pharmacological action and identification of the active principle, and subsequent elucidation of mechanism of action. In the case of Indian plants in the 20th century this process sometimes took almost 50 years. Reserpine and its mechanisms are given in detail, and its current relevance to public health discussed. The foundation of present day methods of pharmacology is briefly presented so the complexity of methods used to identify properties of Ayurveda derived drugs like forskolin and baicalein, and their bioavailability, may be better appreciated. Ayurveda derived anti-oxidants and their levels of action, immuno-modulators, particularly with respect to the NF-kB pathway and its implications for cancer control, are all considered. The example of curcumin derived from turmeric is explained in more detail, because of its role in cancer prevention. Finally, the paper emphasizes the importance of Ayurveda’s concepts of rasayana as a form of dietary chemo-prevention; the significance of ahar, diet, in Ayurveda’s aspiration to prevent disease and restore health thus becomes clear. Understood in this light, Ayurveda may transcend pharmacology as a treatment paradigm.
ABSTRACT
As a major organ of intermediary metabolism, the liver is exposed to a variety of metabolic insults due to diseases and xenobiotics viz., insulin resistance (IR) drugs, toxins, microbial products, etc. One of the consequences of these metabolic insults including obesity and type 2 diabetes mellitus is the development of non-alcoholic fatty liver disease (NAFLD). The recent alarming increase in the prevalence of NAFLD compels the need to develop an appropriate animal model of the disease so as to evolve effective interventions. In this study, we have developed, in the rat, a new model of NAFLD showing several key features akin to the disease in humans. Male Wistar rats were challenged with 30% high fat diet (HFD) – butter, for 2 weeks to induce NAFLD. A hydroalcoholic extract of Picrorhiza kurroa was administered to study the possible reversal of fatty changes in the liver. The extract was given in two doses viz., 200mg/kg and 400 mg/kg b.i.d., p.o. for a period of 4 weeks. There were three control groups (n = 6/group) – vehicle with a regular diet, vehicle with HFD, and HFD with silymarin – a known hepatoprotective. Histopathology showed that the P. kurroa extract brought about a reversal of the fatty infiltration of the liver (mg/g) and a lowering of the quantity of hepatic lipids (mg/g) compared to that in the HFD control group (38.33 ± 5.35 for 200mg/ kg; 29.44 ± 8.49 for 400mg/kg of P. kurroa vs.130.07 ± 6.36mg/g of liver tissue in the HFD control group; P<0.001). Compared to the standard dose of the known hepatoprotective silymarin, P. kurroa reduced the lipid content (mg/g) of the liver more significantly at the dose of 400mg/kg (57.71 ± 12.45mg/kg vs. 29.44 ± 8.49 for the silymarin group vs. 400mg/kg of P. kurroa, P<0.001). In view of the increasing prevalence of metabolic syndrome and NAFLD, P. kurroa should be investigated by the reverse pharmacology path as a potential drug for the treatment of NAFLD, and essential safety studies and preformulation research for concentration of the putative actives should be carried out.
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The pharmaceutical industry is facing serious challenges as the drug discovery process is becoming extremely expensive, riskier and critically inefficient. A significant shift from single to multi targeted drugs especially for polygenic syndromes is being witnessed. Strategic options based on natural product drug discovery, ethnopharmacology and traditional medicines are re-emerging to offer good base as an attractive discovery engine. Approaches based on reverse pharmacology may offer efficient development platforms for herbal formulations. Relevant case studies from India and other countries where such approaches have expedited the drug discovery and development process by reducing time and economizing investments with better safety are discussed.
ABSTRACT
G protein-coupled receptors(GPCRs) are the largest and most diverse group of trans-membrane proteins involved in signal transduction. They have been playing key roles in drug discover-y. Increasing orphan GPCRs (oGPCRs) whose endogenous ligands and functions are still to be identified have been discovered in recent years. It is obvious that oGPCRs might be the most important targets for innovating drugs.