Comparative evaluation of A1A2 and A2A2 cow milk-containing diets on biochemical and histological parameters of Wistar rats.

This Research Communication aims to compare the effect of A1A2 and A2A2 cow milk diets on the biochemical and histological parameters of rats. The rats were divided into four groups and fed with a normal diet, A2 milk powder, A1A2 or A2A2 cow milk diets for 90 d. Blood glucose, kidney function, liver function and lipid profile were examined during the experimental period. The study showed an increase in the body weight of the A1A2 group whereas a slight decrease in the A2A2 group, and blood glucose levels increased from d 0 to day 90 in all experimental groups. However, none of these changes were found to be statistically insignificant (P > 0.05). Moreover, no significant changes were recorded in other parameters (serum glutamic pyruvic transferase and serum glutamic-oxaloacetic transaminase for liver function, bilirubin direct, cholesterol, triglycerides, creatinine and uric acid). The histology of the liver, kidney and pancreas also showed no changes in all groups. Overall, this study revealed no significant difference in the nutritional values of A1A2 and A2A2 milk types and hence equally beneficial for health. Although the present study showed no significant difference in the effect of both milk types in 90 d, further studies might be conducted to evaluate their longer term effects.

Mechanism insights of curcumin and its analogues in cancer: An update.

Cancer is the world's second leading cause of mortality and one of the major public health problems. Cancer incidence and mortality rates remain high despite the great advancements in existing therapeutic, diagnostic, and preventive approaches. Therefore, a quest for less toxic and more efficient anti-cancer strategies is still at the forefront of the current research. Traditionally important, curcumin commonly known as a wonder molecule has received considerable attention as an anti-cancer, anti-inflammatory, and antioxidant candidate. However, limited water solubility and low bioavailability restrict its extensive utility in different pathological states. The investigators are making consistent efforts to develop newer strategies to overcome its limitations by designing different analogues with better pharmacokinetic and pharmacodynamic properties. The present review highlights the recent updates on curcumin and its analogues with special emphasis on various mechanistic pathways involved in anti-cancer activity. In addition, the structure-activity relationship of curcumin analogues has also been precisely discussed. This article will also provide key information for the design and development of newer curcumin analogues with desired pharmacokinetic and pharmacodynamic profiles and will provide in depth understanding of molecular pathways involved in the anti-cancer activities.

Recent Developments and Potential for Clinical Use of Casein as a Drug Carrier.

BACKGROUND: The development of drug delivery carriers is the key area of research in the field of novel drug delivery systems. To date, a long list of carriers has been identified for this purpose but the deliveries of poorly water-soluble active substances are still facing challenges and hence, such substances are pharmacologically unsafe and economically incompetent. OBJECTIVE: This article aims to review the applications of casein as a drug carrier and its potential for clinical use. METHODS: The relevant literature on the casein protein was collected from authentic online scientific databases like PubMed, Scopus and Google Scholar using different keywords including "casein", "drug delivery system", "drug carrier" and "bioavailability". The articles and books accessed online have been thoroughly reviewed and the most relevant reports on casein as a drug carrier have only been included in the present study. RESULTS: Casein is a milk protein that has many structural and physicochemical properties which facilitate its functionality in delivery systems. Moreover, its amphiphilic nature makes it the most suitable carrier for both hydrophobic and hydrophilic drugs without showing any toxic effects. The carriers obtained from natural sources are trustworthy over synthetic carriers and in the demand of the market due to their easy availability, low-cost factor, bio-friendly and nontoxic nature. CONCLUSION: Casein was found to be an effective natural drug carrier in various delivery systems due to its unique applications in improving the bioavailability and efficacy of a drug.

Formulation and evaluation of SGLT2 inhibitory effect of a polyherbal mixture inspired from Ayurvedic system of medicine.

Background and aim: The ingredients viz., Artemisia roxburghiana, Cissampelos pareira, Stephania glabra, Drimia indica, Roylea cinerea, Tinospora sinensis and Curcuma longa of the present formulation are used to treat diabetes in the Indian traditional medical system. Adopting the concept of multiple herbal mixtures for better therapeutic effects from the ancient Ayurvedic text Sarangdhar Samhita, the present study aimed to develop a polyherbal formulation (PHF) of seven herbs and to evaluate its sodium-glucose cotransporter protein-2 (SGLT2) inhibitory effect on type 2 diabetic rats. Experimental procedure: Streptozotocin (STZ) (60 mg/kg) and nicotinamide (NAM) (120 mg/kg) were intraperitoneally administered to induce type 2 diabetes in Wistar rats. The animals were divided into 5 groups viz. normal control, diabetic control, positive control (dapagliflozin at 0.1 mg/kg) and two test groups (PHF at 250 and 500 mg/kg). Various parameters including blood glucose, serum glutamic pyruvic transaminase (SGPT), serum glutamic-oxaloacetic transaminase (SGOT), bilirubin, triglycerides and creatinine were measured. Results and conclusion: The treatment with PHF (250 and 500 mg/kg) showed a significant (p < 0.05) decrease in blood glucose levels by 56.37% and 58.17%, respectively. The levels of SGOT, SGPT and bilirubin were significantly reduced in PHF-fed diabetic rats. Histopathological examination revealed no major changes in the treated groups as compared to the normal control. The molecular docking study showed strong binding of ß-sitosterol, insulanoline, warifteine, dehydrocorydalmine, taraxerol acetate, lupeol, corydalmine and luteolin to SGLT2 protein. The present study concludes that PHF has promising antidiabetic activity via inhibiting SGLT2 protein without showing any adverse effects.

Ameliorating potential of curcumin and its analogue in central nervous system disorders and related conditions: A review of molecular pathways.

Curcumin, isolated from turmeric (Curcuma longa L.) is one of the broadly studied phytomolecule owing to its strong antioxidant and anti-inflammatory potential and has been considered a promising therapeutic candidate in a wide range of disorders. Considering, its low bioavailability, different curcumin analogs have been developed to afford desired pharmacokinetic profile and therapeutic outcome in varied pathological states. Several preclinical and clinical studies have indicated that curcumin ameliorates mitochondrial dysfunction, inflammation, oxidative stress apoptosis-mediated neural cell degeneration and could effectively be utilized in the treatment of different neurodegenerative diseases. Hence, in this review, we have summarized key findings of experimental and clinical studies conducted on curcumin and its analogues with special emphasis on molecular pathways, viz. NF-kB, Nrf2-ARE, glial activation, apoptosis, angiogenesis, SOCS/JAK/STAT, PI3K/Akt, ERK1/2 /MyD88 /p38 MAPK, JNK, iNOS/NO, and MMP pathways involved in imparting ameliorative effects in the therapy of neurodegenerative disorders and associated conditions.

Role of curcumin in ameliorating hypertension and associated conditions: a mechanistic insight.

Curcumin, belongs to the curcuminoid family, is a natural phenolic compound, presenting low bioavailability and pleiotropic activity. Since ancient times, curcumin has been in use as food spices and folk remedy to treat cough, cold, cuts and wounds, and skin diseases. Preclinical and clinical studies have indicated that curcumin acts a promising therapeutic agent in the management of a wide array of health issues, viz., hyperlipidemia, metabolic syndrome, anxiety, arthritis, cancer and inflammatory diseases. Owing to its enormous potential, recent research has been focused on the synthesis of curcumin and its analogues for the management of metabolic disorders. In the current scenario, hypertension is considered as a key risk factor due to its involvement in various pathogeneses. Mechanistically, curcumin and its analogues like hexahydrocurcumin, tetrahydrocurcumin, etc. have been reported to elicit anti-hypertensive effect through diverse signalling pathways, viz., pathway mediated by Nrf2-ARE, NF-kB, NO/cGMP/PDE5/MMPs, RAAS/ACE, HAT/HDAC, G0/G1/apoptosis, CYP3A4, UCP2/PARP, VEGF/STAT/AXL/tyrosine kinase and TGF-ß/Smad-mediated pathways. Thus, the present review has been aimed to highlight different molecular pathways involved in the amelioration of hypertension and associated conditions.

Recent advances in immunotoxicity and its impact on human health: causative agents, effects and existing treatments.

BACKGROUND: A strong immune system is a primary requirement to keep the body safe from different ailments and infections. A human knowingly or unknowingly often comes to the exposure of many foreign substances such as pollutants, chemicals, metals and drugs that affect the immune system. Though some of these substances are known to exert immunotoxicity, their precise role as immunotoxicant is still unidentified, hence, the testing of these substances has to be taken into account. The present manuscript aimed to explore the mechanism behind immunotoxicity, biomarkers involved, manifestations, testing of immunotoxicity and its management. METHODS: Relevant literature on immunotoxicity, collected from online scientific databases like Scopus, PubMed and Google Scholar, was rigorously reviewed. RESULTS: Earlier reports showed that immunotoxic effects of chemicals and pharmaceuticals may cause various health problems including allergic reactions, skin disorders, respiratory infections, gastrointestinal problems, and autoimmune disorders. If diagnosed in time, many of these conditions can be managed with the help of existing treatments although the complete treatment is sometimes a big challenge. CONCLUSION: Based on the review of available literature, it can be concluded that immunotoxicity is one of the key factors responsible for several infectious diseases, autoimmune disorders and even cancers. Hence, the requirement of advanced diagnostic tools and established treatments for immunotoxicity is highly recommended.

Modulation of gut microbiota with Ayurveda diet and lifestyle: A review on its possible way to treat type 2 diabetes.

Background: The prevalence of type 2 diabetes (T2D) has increased substantially in the past few decades throughout the world. In India, the epidemic of diabetes continues to increase irrespective of area, status, and age. Despite various scientific societies involved in the treatment of diabetes, still, the burden of diabetes keeps growing. Aims: The aim of this work is to explore the Ayurvedic concept of a personalized diet to modulate the gut microbiota for the treatment of T2D. Material and methods: A thorough study of literature from online scientific databases including Web of Science, PubMed, Scopus, and Google Scholar as well as from classical texts of Ayurveda was done. A careful compilation was done to extract the valuable output of the personalized diet to modulate the gut microbiota. Results: There are various diets used to control blood glucose levels, and their effects are also being studied on the transcriptome or epigenome despite 99.9% genomic similarity among human beings. However, microbiomes have only 10% similarity. Ayurvedic diet is given on the basis of Prakriti (body constitution), therefore, it is also called personalized diet. Conclusion: The diets prescribed for T2D in Ayurveda are high in fibers, polyphenols, and complex carbohydrates which enrich butyrate-producing bacteria and decrease lipopolysaccharide-producing bacteria. Hence, there is a need to have a personalized diet to manage the glucose level by enriching beneficial gut microbiota. The approach of a personalized diet associated with gut microbiota can be helpful in maintaining blood sugar in T2D patients.

Antidiabetic effect of aqueous-ethanol extract from the aerial parts of Artemisia roxburghiana.

Artemisia roxburghiana is used for the management of diabetes mellitus in the Indian subcontinent. The present work aimed to validate the traditional claim of the plant in diabetes mellitus. In vitro studies were conducted using α-glucosidase and α-amylase assays whereas streptozotocin-nicotinamide-induced diabetic Wistar rats were used for in vivo study. The aqueous-ethanol extract from the aerial parts was found to exhibit α-glucosidase and α-amylase inhibitory activities with the IC50 values of 31.0 and 17.2 mg/mL, respectively when compared with acarbose (IC50 = 8.6 and 16.25 mg/mL, respectively). The extract showed a significant glucose-lowering effect in diabetic rats at the doses of 200 and 400 mg/kg in a dose-dependent manner, while acarbose (10 mg/kg) was used as a standard. The results revealed that A. roxburghiana aerial parts showed antidiabetic activity via inhibiting α-glucosidase and α-amylase enzymes. The present study also validated the ethnomedicinal claim of the plant in diabetes mellitus.

Emodin - A natural anthraquinone derivative with diverse pharmacological activities.

Emodin (1,3,8-trihydroxy-6-methyl-anthraquinone) is a natural anthraquinone derivative that is present in numerous globally renowned herbal medicines. It is recognised as a protein tyrosine kinase inhibitor and as an anticancer drug, active against various tumour cells, including lung, breast, liver, and ovarian cancer cells. Recently, its role in combination chemotherapy with various allopathic medicines, to minimize their toxicity and to enhance their efficacy, has been studied. The use of emodin in these therapies is gaining popularity, due to fewer associated side effects compared with standard anticancer drugs. Emodin has a broad therapeutic window, and in addition to its antineoplastic activity, it displays anti-ulcer, anti-inflammatory, hepatoprotective, neuroprotective, antimicrobial, muscle relaxant, immunosuppressive and antifibrotic activities, in both in vitro and in vivo models. Although reviews on the anticancer activity of emodin have been published, none coherently unite all the pharmacological properties of emodin, particularly the anti-oxidant, antimicrobial, antidiabetic, immunosuppressive and hepatoprotective activities of the compound. Hence, in this review, all of the available data regarding the pharmacological properties of emodin are explored, with particular emphasis on the modes of action of the molecule. In addition, the manuscript details the occurrence, biosynthesis and chemical synthesis of the compound, as well as its toxic effects on biotic systems.

Curcumin: An Insight into Molecular Pathways Involved in Anticancer Activity.

Curcuma longa has been mentioned in the Indian system of medicine for the management of a wide range of diseases. C. longa and its metabolites like curcumin, ar-turmerone, methylcurcumin, demethoxy-curcumin, and bisdemethoxycurcumin have also been reported to be beneficial in various types of cancer. Curcumin elicits anticancer properties chiefly by triggering apoptotic pathways in cancer cells. The properties are facilitated through diverse signaling pathways viz. pathways mediated by NF-kB, WNT/ß-catenin pathway COX-2, LOX, STAT3, prostaglandin E2, phosphorylase kinase, VEGF, AKT, AP1, STAT3, PI3K, Akt, mTOR, ERK5, AP-1, TGF-b, PPARc, EBPa, NLRP3 inflammasome, p38MAPK, Nrf2, Notch-1, AMPK, TLR-4, etc. The present article highlights curcumin biosynthesis, phytochemistry and diverse molecular pathways involved in regulating several types of secondary messengers to exhibit anticancer activity in almost all the forms of cancer.

Formulation and Evaluation of Polyherbal Cream and Lotion for the Treatment of Psoriasis-Induced Secondary Infections.

BACKGROUND: Psoriasis is one of the most common skin diseases in humans and affects a major population worldwide. The aim of the present study is to evaluate the efficacy of selected polyherbal formulations against psoriasis-induced secondary infections. AIM: Psoriasis is one of the most common skin diseases in humans and affects a major population worldwide. The aim of the present study is to evaluate the efficacy of selected polyherbal formulations against psoriasis-induced secondary infections. METHODS: Samples were collected from the scalp, behind the ears, chest and back of the patients. The microscopic examination of fungal and bacterial growth was carried out with lactophenol cotton blue stain and gram stain, respectively. Volatile constituents of essential oils were identified by GC-MS analysis, in order to investigate the relation between chemical composition and biological activity. Nutrient agar media was used for antibacterial activity whereas Sabourauds dextrose agar media was used for antifungal activity. RESULTS: A total of 24 isolates were obtained from 2 patients of scalp psoriasis. Anti-oxidant activity of the samples was determined using DPPH radical scavenging method. In the present study, EOs showed a good antifungal action against Malassezia pachydermatis and other microbial strains. The GC-MS analysis revealed the presence of eugenol, linalool, citral, neral, limonene, terpenes, eucalyptol and thymol in the essential oils. The formulated retention lotion 1 (L4), 2 (L5), 3 (L6) and Cream 1 (C1) showed DPPH radical scavenging activity by 23.52%, 24.48%, 28% and 5.08%, respectively. CONCLUSION: The present study concluded that most of the formulated lotions and creams showed good antimicrobial activity and may be applied topically against scalp psoriasis.

Protective and therapeutic effects of natural products against diabetes mellitus via regenerating pancreatic ß-cells and restoring their dysfunction.

Diabetes mellitus is a growing public health concern and an increasing interest has been raised to search for new compounds with therapeutic effects on ß-cells. There are chronic insulin resistance and loss of ß-cell mass in the case of type-2 diabetes which covers about 90% of total diabetic patients. This work aims to critically review the protective and regenerative effects of various antidiabetic natural products on pancreatic ß-cells. A thorough literature survey was conducted on the natural molecules and extracts having a protective, regenerative, and repairing effect on ß-cells. The primary source of the literature was online scientific databases such as PubMed, Scopus, and Google Scholar. Besides, selected relevant textbooks were also consulted. Various natural molecules including berberine, curcumin, mangiferin, stevioside and capsaicin, and extracts obtained from the plants like Capsicum annum, Gymnema sylvestre, Stevia rebaudiana and Nymphaea stellate, were found to produce regenerative and anti-apoptosis effects on ß-cells. These natural products were also found to increase insulin secretion by stimulating ß-cells. The present review concluded that a large number of molecules and extracts, abundantly found in nature, possess antidiabetic effect via targeting ß-cells. Further research is warranted to use these agents as a drug against diabetes.

A Molecular Approach on the Protective Effects of Mangiferin Against Diabetes and Diabetes-related Complications.

BACKGROUND: Diabetes and its related complications are now a global health problem without an effective therapeutic approach. There are many herbal medicines which have attracted much attention as potential therapeutic agents in the prevention and treatment of diabetic complications due to their multiple targets. AIM: The aim of this study is to review available knowledge of mangiferin focusing on its mode of action. METHODS: Mangiferin was extensively reviewed for its antidiabetic activity using online database like Scopus, PubMed, and Google Scholar as well as some offline textbooks. A critical discussion based on the mechanism of action and the future perspectives is also given in the present manuscript. RESULTS: Mangiferin is a natural C-glucoside and mainly obtained from its primary source, the leaves of mango tree (Mangifera indica L.). Therapeutic and preventive properties of mangiferin include antimicrobial, anti-inflammatory, antioxidative, antiallergic, neuroprotective, and cognition-enhancing effects. It dissolves well in water, so it can be easily extracted into infusions and decoctions and hence, a number of researches have been made on the therapeutic effect of this molecule. Recently, mangiferin has been proved to be an effective remedy in diabetes and diabetes-related complications. It is a beneficial natural compound for type 2 diabetes mellitus as it improves insulin sensitivity, modulates lipid profile and reverts adipokine levels to normal. CONCLUSION: This study concludes that mangiferin has the potential to treat diabetes and it can be developed as a therapeutic agent for diabetes and the complications caused by diabetes.

Drimia indica: A Plant Used in Traditional Medicine and Its Potential for Clinical Uses.

Drimia indica (Roxb.) Jessop (Asparagaceae) is a reputed Ayurvedic medicine for a number of therapeutic benefits, including for cardiac diseases, indigestion, asthma, dropsy, rheumatism, leprosy, and skin ailments. The present work aimed to critically and extensively review its traditional uses, phytochemistry, pharmacology, toxicology, and taxonomy together with the mechanisms of action of selected extracts of D. indica. A systematic literature survey from scientific databases such as PubMed, Scopus, and Web of Science as well as from some textbooks and classical texts was conducted. The plant, mainly its bulb, contains various bioactive constituents, such as alkylresorcinols, bufadienolides, phytosterols, and flavonoids. Various scientific studies have proven that the plant has anthelmintic, anticancer, antidiabetic, antimicrobial, antioxidant, and wound healing activities. The present work concludes that D. indica has the potential to treat various diseases, mainly microbial infections. This review also suggests that bufadienolides, flavonoids, and steroids might be responsible for its bioactive potential.

Status of Indian medicinal plants in the International Union for Conservation of Nature and the future of Ayurvedic drugs: Shouldn't think about Ayurvedic fundamentals?

The present market for herbal drugs is estimated about ₹40 billion, which is expected to increase by 16% in next 3-4 years. The current production of many Ayurvedic herbs is less than their market demand, which incentivizes adulteration in the Ayurvedic drug supply chain. The present work aims to highlight the most used Ayurvedic plants that have been listed in the International Union for Conservation of Nature's "red list" of endangered or vulnerable plants. The future of Ayurvedic medicines from these listed plants is uncertain, as the collection of herbs from their natural habitat is prohibited and their cultivation does not meet market demands. Many of these plants, such as Taxus baccata and T. wallichiana, are endangered and are only grown in their natural habitats; their cultivation in other areas is impractical. This is the present state, and will worsen as demand continues to grow, with increasing populations and increasing adoption of this system of medicine. It is possible that in coming years most of the Ayurvedic drugs will be adulterated, and will cause only side effects rather than the therapeutic effects. The Ayurvedic fundamentals are under-explored areas where the Ayurvedic practitioners and research scientists can work together. The scientific work on the basic principles will unravel many unknown or little-known facts of this ancient science. Hence, the present review emphasizes the conservation of Ayurvedic herbs, minimization of the use of medicinal plants and the promotion of the research based on Ayurvedic fundamentals.

Ethnomedicinal Investigation of Medicinal Plants of Chakrata Region (Uttarakhand) Used in the Traditional Medicine for Diabetes by Jaunsari Tribe.

The Himalayan region is the treasure house of natural wealth, particularly of medicinal and aromatic plants. These plants are used by the Indian traditional healers for the past many centuries to treat various ailments such as skin disorders, asthma, diabetes, snake bite, fever, pain, eye diseases, diarrhoea, indigestion, jaundice, burn, wound, liver disorder, CNS disorders and urinary tract infection. The indigenous traditional knowledge of medicinal plants and therapies of various local communities has been lost due to changes in traditional culture and the introduction of modern technologies. Therefore, it is essential to explore the traditional knowledge of the indigenous medicinal plants mainly in such areas where there is a severe threat to natural vegetation owing to human inhabitation. The present study aimed to explore the medicinal plants of Chakrata region (Jaunsar-Bawar Hills), Uttarakhand, India used in the folk medicine for the management of diabetes by Jaunsari Tribe. In a comprehensive field survey, the information about the medicinal plants have been mainly collected from the traditional healers and other elderly people belong to the tribal community. All the information about the medicinal plants of the study area was documented in a field book. Various tools have been used to collect the samples for identification purpose and the authentication of the plants was done with the help of taxonomists. The literature on these plants was also searched from online (PubMed and Scopus) as well as from some textbooks and Ayurvedic classical texts. The present survey-based work described a total of 54 plants belonging to 47 genera and 30 families used in the traditional medicine for the management of diabetes in Chakrata region. The information gathered from the local community revealed that the plants are effective in diabetes and one can use most of them without consulting a practitioner or traditional healer. The literature revealed that most of the surveyed plants are already used in the preparation of various antidiabetic formulations such as Chandraprabha vati, Nishamalaki chunra, Amritamehari churna and Nisakathakadi kashayam along with various patent drugs which are frequently prescribed by the Ayurvedic practitioners in India. The present study explored the traditional as well as scientific knowledge on the antidiabetic plants used by the tribal community. The documented information on these plants can be further used by the scientific community to develop new drugs/formulations with the help of modern techniques.

Yoga Practice Improves the Body Mass Index and Blood Pressure: A Randomized Controlled Trial.

BACKGROUND: Yoga, an ancient Indian system of exercise and therapy is an art of good living or an integrated system for the benefit of the body, mind, and inner spirit. Regular practice of yoga can help to increase blood flow to the brain, reduce stress, have a calming effect on the nervous system, and greatly help in reducing hypertension. AIM: Aim of the present study is to evaluate the effect of 1-month yoga practice on body mass index (BMI), and blood pressure (BP). MATERIALS AND METHODS: The present study was conducted to determine the effect of yoga practice on 64 participants (age 53.6 ± 13.1 years) (experimental group) whereas the results were compared with 26 healthy volunteers (control group). We examined the effects of yoga on physiological parameters in a 1-month pilot study. Most of the participants were learner and practiced yoga for 1 h daily in the morning for 1 month. BMI and BP (systolic and diastolic) were studied before and after 1 month of yoga practice. RESULTS: Yoga practice causes decreased BMI (26.4 ± 2.5-25.22 ± 2.4), systolic BP (136.9 ± 22.18 mmHg to 133 ± 21.38 mmHg), and diastolic BP (84.7 ± 6.5 mmHg to 82.34 ± 7.6 mmHg). On the other hand, no significant changes were observed in BMI and BP of control group. CONCLUSION: This study concludes that yoga practice has potential to control BMI and BP without taking any medication.

Combined Treatment with CCI779 and SB203580 Induces Cellular Senescence in Renal Cell Carcinoma Cell Line via p53 Pathway.

BACKGROUND: Renal cell carcinoma (RCC) is one of the most common neoplasms that occurs in the kidney and is marked by a unique biology, with a long history of poor response to conventional cancer treatments. In recent years, there have been significant advancements implemented to understanding the biology of RCC, which has led to the introduction of novel targeted therapies in the management of patients with metastatic disease. OBJECTIVE: The present study was designed to evaluate the effects of p38 MAPK inhibitor (SB203580), alone and in combination with mTOR inhibitor (CCI779) on apoptosis and cell proliferation. METHOD: Subtoxic concentrations of inhibitors were selected by MTT assay using A-498, ACHN and primary culture of RCC. RESULTS: All the three types of RCC cells had almost similar response towards these inhibitors. The results revealed that 25µM of SB203580 and 20µM of CCI779 at 48 hrs decreased cell viability by 20% and 30%, respectively, whereas the combination of both inhibitors showed a maximum of 40% reduction in cell viability. CONCLUSION: The study concludes that the combination of SB203580 and CCI779 inhibitors may induce cellular senescence in A-498 cells with higher potency than that of individual inhibitors.

Ayurvedic concept of Shatkriyakala: a traditional knowledge of cancer pathogenesis and therapy.

The term Kriyakala refers to the recognition of the stage of a disease's progress, which helps to determine appropriate measure to correct the imbalance in Doshas (biological factors). It is a compound expression, comprised of Kriya and Kala, where Kriya means the choice to treatment (medicine, food and daily-routine) used to improve the disturbance in Doshas, and Kala refers to the stage of progress of a disease. Sushruta, an ancient Indian surgeon, has described the concept of Kriyakala in Varnaprashnadhyaya, an ancient Vedic Sanskrit text, which seeks to explain the incidence of Varnas in terms of Doshic disturbances. Varna, in modern parlance, may be described as an inflammatory process that may lead ulceration and chronic inflammation, promoting all stages of carcinogenesis. Abnormal interactions between Prakriti (genotype) and environmental factors vitiate the Doshas and impair immunity, which can lead to aberrant cell growth and cancer. Moreover, the interaction between vitiated Doshas and weak Dhatus (body tissues) manifests as cancers of a specific organ. Shatkriyakala (six stages of progress of a disease), on the other hand, provides a framework to assess the cancer and its pathogenesis in different stages. According to Ayurvedic concepts, all cancer therapies treat the affected tissues indirectly by eliminating vitiated Doshas, rejuvenating Dhatus and restoring immunity in cancer patients. The present review describes the six stages of Shatkriyakala in detail, with an emphasis on research areas to validate the concept of Shatkriyakala. This traditional knowledge can be utilized with modern technologies to detect predisposition for cancer or diagnose cancer in its early stages.