Untargeted metabolomics reveals alterations in metabolites of lipid metabolism and immune pathways in the serum of rats after long-term oral administration of Amalaki rasayana.

Amalaki rasayana, a traditional preparation, is widely used by Ayurvedic physicians for the treatment of inflammatory conditions, cardiovascular diseases, and cancer. Metabolic alterations induced by Amalaki rasayana intervention are unknown. We investigated the modulations in serum metabolomic profiles in Wistar rats following long-term oral administration of Amalaki rasayana. Global metabolic profiling was performed of the serum of rats administered with either Amalaki rasayana (AR) or ghee + honey (GH) for 18 months and control animals which were left untreated. Amalaki rasayana components were confirmed from AR extract using HR-LCMS analysis. Significant reductions in prostaglandin J2, 11-dehydrothromboxane B2, and higher levels of reduced glutathione and glycitein metabolites were observed in the serum of AR administered rats compared to the control groups. Eleven different metabolites classified as phospholipids, glycerophospholipids, glucoside derivatives, organic acids, and glycosphingolipid were exclusively observed in the AR administered rats. Pathway analysis suggests that altered metabolites in AR administered rats are those associated with different biochemical pathways of arachidonic acid metabolism, fatty acid metabolism, leukotriene metabolism, G-protein mediated events, phospholipid metabolism, and the immune system. Targeted metabolomics confirmed the presence of gallic acid, ellagic acid, and arachidonic acid components in the AR extract. The known activities of these components can be correlated with the altered metabolic profile following long-term AR administration. AR also activates IGF1R-Akt-Foxo3 signaling axis in heart tissues of rats administered with AR. Our study identifies AR components that induce alterations in lipid metabolism and immune pathways in animals which consume AR for an extended period.

Simultaneous use of oxalate-degrading bacteria and herbal extract to reduce the urinary oxalate in a rat model: A new strategy.

OBJECTIVE: Urinary stones with oxalate composition can cause kidney failure. Recent findings evidenced that probiotics are effective in reducing oxalate absorption in these subjects based on their high colonic absorption levels at baseline. The purpose of this study was to evaluate the effect of the simultaneous use of oxalate-degrading bacteria, Urtica dioica and T. terrestris extract in reducing urinary oxalate. MATERIALS AND METHODS: Anti-urolithiatic activity of Urtica dioica and T. terrestris extract and pro-biotic by using ethylene glycol induced rat model. In this study, 4 strains of Lactobacillus and 2 strains of Bifidobacterium and also 2 strains of L. paracasei (that showed high power in oxalate degrading in culture media) were used. Male Wistar rats were divided into four groups (n=6). The rats of group-I received normal diet (positive control group) and groups-II (negative control group), III, IV rats received diet containing ethylene glycol (3%) for 30 days. Groups III rats re-ceived Urtica dioica and T. terrestris extract. Groups IV rats received extracts + probiotic for 30 days. FINDINGS: The results show that the use of herbal extracts (Urtica dioica and T. terrestris) redu-ced the level of urinary oxalate and other parameters of urine and serum. Also, the accumulation of calcium oxalate crystals in the kidney tissue was significantly reduced. CONCLUSION: Considering that the formation of calcium oxalate crystals can cause inflammation and tissue damage in the kidney, the use of herbal extracts with oxalatedegrading bacteria can be a new therapeutic approach to preventing the formation of kidney stones.

Leptadenia reticulata (Retz.) Wight & Arn. (Jivanti): Botanical, Agronomical, Phytochemical, Pharmacological, and Biotechnological Aspects.

Leptadenia reticulata (Retz.) Wight & Arn. (Apocynaceae), is a traditional medicinal plant species widely used to treat various ailments such as tuberculosis, hematopoiesis, emaciation, cough, dyspnea, fever, burning sensation, night blindness, cancer, and dysentery. In Ayurveda, it is known for its revitalizing, rejuvenating, and lactogenic properties. This plant is one of the major ingredients in many commercial herbal formulations, including Speman, Envirocare, Calshakti, Antisept, and Chyawanprash. The therapeutic potential of this herb is because of the presence of diverse bioactive compounds such as α-amyrin, ß-amyrin, ferulic acid, luteolin, diosmetin, rutin, ß-sitosterol, stigmasterol, hentricontanol, a triterpene alcohol simiarenol, apigenin, reticulin, deniculatin, and leptaculatin. However, most biological studies on L. reticulata are restricted to crude extracts, and many biologically active compounds are yet to be identified in order to base the traditional uses of L. reticulata on evidence-based data. At present, L. reticulata is a threatened endangered plant because of overexploitation, unscientific harvesting, and habitat loss. The increased demand from pharmaceutical, nutraceutical, and veterinary industries has prompted its large-scale propagation. However, its commercial cultivation is hampered because of the non-availability of genuine planting material and the lack of knowledge about its agronomical practices. In this regard, micropropagation techniques will be useful to obtain true-to-type L. reticulata planting materials from an elite germplasm to meet the current demand. Adopting other biotechnological approaches such as synthetic seed technology, cryopreservation, cell culture, and genetic transformation can help conservation as well as increased metabolite production from L. reticulata. The present review summarizes scientific information on the botanical, agronomical, phytochemical, pharmacological, and biotechnological aspects of L. reticulata. This comprehensive information will certainly allow better utilization of this industrially important herb towards the discovery of lead drug molecules.

Epigenomic maintenance through dietary intervention can facilitate DNA repair process to slow down the progress of premature aging.

DNA damage caused by various sources remains one of the most researched topics in the area of aging and neurodegeneration. Increased DNA damage causes premature aging. Aging is plastic and is characterised by the decline in the ability of a cell/organism to maintain genomic stability. Lifespan can be modulated by various interventions like calorie restriction, a balanced diet of macro and micronutrients or supplementation with nutrients/nutrient formulations such as Amalaki rasayana, docosahexaenoic acid, resveratrol, curcumin, etc. Increased levels of DNA damage in the form of double stranded and single stranded breaks are associated with decreased longevity in animal models like WNIN/Ob obese rats. Erroneous DNA repair can result in accumulation of DNA damage products, which in turn result in premature aging disorders such as Hutchinson-Gilford progeria syndrome. Epigenomic studies of the aging process have opened a completely new arena for research and development of drugs and therapeutic agents. We propose here that agents or interventions that can maintain epigenomic stability and facilitate the DNA repair process can slow down the progress of premature aging, if not completely prevent it. © 2016 IUBMB Life, 68(9):717-721, 2016.

Ayurveda and Yoga management of chronic alcoholism sequelae - A case report.

Alcohol has always been a component in the dietary pattern of human civilization. It is widely used in society for celebration and socialization. Alcohol abuse is among the most serious problems in public health characterized by uncontrolled drinking which causes physical and emotional dependence on alcohol. Chronic alcoholics are at a higher risk of developing vitamin B1 deficiency due to malabsorption, poor diet, and an increased demand for nutrition. Vitamin B1(Thiamine) is an essential nutrient required for the body's energy metabolism and proper functioning of the nervous system. A person who excessively consumes madya (alcohol) and then abruptly discontinues drinking and takes recourse to drinking excess madya once again, suffers from Madatyaya Upadrava(chronic alcoholism) that is Vikshay. Here is a case report of an alcoholic patient who ceased drinking and then resumed alcohol in large amounts. He presented with symptoms of generalized weakness, body ache, aphasia, confusion, fever (on and off), thirst, cough, headache, and numbness. The patient underwent a two-month treatment regimen that combined Satvavajay Chikitsa, Yoga, and Shaman Chikitsa involving Rasayana medications and procedures including snehan (Oleation), swedan (fomentation), nabhi puran (filling oil with navel), nasya (nasal administration), shirodhara (continuous flow of liquid on head) and basti (medicated enema). The intervention outcome showed relief from the aforementioned symptoms and improvement in both symptoms and GCS(Glasgow coma scale) score. This treatment approach aimed to promote vitality, longevity, and an overall sense of balance and well-being. There are not many corroborating cases being reported and managed with Ayurveda. This case report highlights transforming health through the cumulative effects of Rasayana medicines, panchakarma, and yoga.

Ethnopharmacological validation of Karkataka Taila-An edible crab Rasayana in rotenone-induced in vitro and in vivo models of Parkinson's disease.

ETHNOPHARMACOLOGICAL RELEVANCE: 'Karkataka Taila (KT), an ancient Ayurvedic Rasayana comprising the edible freshwater crab Scylla serrata Forskal flesh, is still used by local traditional practitioners in Kerala state to treat tremors and palsy. In the scientific community, it becomes less exposed due to the lack of adequate scientific validations and brief reports. There has been no published research on the effectiveness of KT in treating Parkinson's disease (PD). PURPOSE: The purpose of the current research work was to investigate the anti-Parkison's potential of KT against rotenone-induced neurotoxicity in SH-SY5Y cell lines and rat model of PD and investigate underlying molecular mechanisms. MATERIALS AND METHODS: The components of KT have been identified by gas chromatography-mass spectroscopy (GC-MS). The neuroprotective activity of KT was assessed using SH-SY5Y cell lines and rats against rotenone-induced PD. The parameters used for asses the neuroprotection are antioxidant markers (ROS and SOD), anti-inflammatory markers (IL-6, IL-1ß, TNF-α, and nitrite), and dopamine levels. Behavioral evaluation and rat brain histopathology were carried out to further support the neuroprotection. RESULT: Analysis using GC-MS revealed 36 constituents in KT. In vitro, the KT displayed considerable neuroprotective effects in terms of decreasing oxidative stress (ROS and SOD), neuroinflammation (IL-6, IL-1ß, TNF-α, and nitrite), and elevating dopamine concentration. In vivo data showing improvements in histopathological and biochemical parameters confirmed the in vitro study findings, and in terms of behavioral assays, KT displayed significant activity. CONCLUSION: GC-MS profiling was used to identify the bioactive compounds of KT with antioxidant, anti-inflammatory, and neuroprotective properties. As a result, they may be responsible for the therapeutic effects of KT on PD.

Computational screening of potential anti-inflammatory leads from Jeevaneeya Rasayana plants targeting COX-2 and 5- LOX by molecular docking and dynamic simulation approaches.

Inflammation plays a pivotal role in various pathological processes, ranging from routine injuries and infections to cancer. Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) are two major enzymes involved in the formation of lipid mediators of inflammation, such as prostaglandins and leukotrienes, through the arachidonic acid pathway. Despite the frequent use of nonsteroidal anti-inflammatory drugs for managing inflammatory disorders by inhibiting these enzymes, there is a wide spectrum of adverse effects linked to their usage. Jeevaneeya Rasayana (JR), a polyherbal formulation traditionally used in India, is renowned for its anti-inflammatory properties. The present study aimed to identify the potential phytocompounds in JR plants against COX-2 and 5-LOX, utilizing molecular docking and dynamic simulations. Among the 429 identified phytocompounds retrieved from publicly available data sources, Terrestribisamide and 1-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine have shown potential binding affinity and favorable interactions with COX-2 and 5-LOX arachidonic acid binding sites. The physicochemical properties and ADMET profiles of these compounds determined their drug-likeness and pharmacokinetics features. Additional validation using molecular dynamics simulations, SASA, Rg, and MM-PBSA binding energy calculations affirmed the stability of the complex formed between those compounds with target proteins. Together, the study identified the effectual binding potential of those bioactive compounds against COX-2 and 5-LOX, providing a viable approach for the development of effective anti-inflammatory medications.

Five years of disease-free survival in a case of recurrent, post-op, grade 3, stage 2, Malignant Spindle Cell Melanoma treated with Ayurvedic medicines: A case report.

Malignant spindle cell melanoma is a rare cancer with a questionable prognosis because of limited published case reports. This article discusses a male patient with a history of Spindle cell melanoma tumor, Rt heel, Grade 3 (Gr 3) Stage 2 (St 2) seen in our OPD treated with supporting herbo-mineral combination of Ayurvedic medicine. Such types of cancers are of concern and can be more troublesome to the patient. The initial chief complaint of the patient was a palpable corn-like growth in the right heel, which was surgically removed at that time. When it recurred after one year, it was investigated thoroughly and it was found malignant, and then operated again. The patient came to us after his second operation. After appropriate analysis based on Ayurvedic and modern parameters, the patient was treated with Ayurved treatment. As there was no other treatment suggested by oncologists, he was on supportive Ayurvedic treatment only. Ayurvedic treatment continued for 2 years afterwards. The treatment module showed complete relief in the symptoms (100%), by the end of treatment. Follow-up PET scans showed further improvement and a complete reversal of residual disease was observed. The last PET scan did not show any evidence of abnormality. To date, there has been no recurrence and the patient has been living completely normally for the last almost 5 years (karnofsky score 90/100). It can be concluded that the addition of Ayurvedic treatment might have helped this patient of malignant spindle cell melanoma for regression of residual disease, prevention of metastasis to date, and a good quality of life. We have observed 5+ years of disease-free survival and near-normal quality of life for this patient, and still ongoing.

Management of Otitis externa with Ayurvedic formulation Gandhak Rasayana- A case report.

Otitis externa is an inflammatory and infectious disease that affects the external auditory canal. The term otorrhea refers to the outflow of discharge from the ear which is one of the main symptoms of otitis externa along with inflammation. External ear canal pathology or middle ear illness with tympanic membrane perforation is the etiological factor of otorrhea. Otorrhea is an indication of infection. Antimicrobial agents are the conventional treatment of various bacterial and fungal infections, but they have impediments such as resistance development, side effects, patient affordability, etc. The Gandhak Rasayana formulation mentioned in the Ayurvedic text can be a good option for the treatment of various infectious diseases. Karnasrava is a type of ear disease referred to as Vata predominant Tridoshaja disease and it is curable. The term Karnasrava signifies discharge from ear and is self-explanatory. Karnasrava consists of a wide spectrum of diseases and can have a near correlation with otitis externa as per signs and symptoms. Gandhak Rasayana exhibited significant antibacterial, antifungal and anti-inflammatory activity in otitis externa. Evaluating its antibacterial and antifungal activity can provide scientific evidence for the study through the present case report. A 31-year-old male patient registered in OPD at Sane Guruji Hospital, Hadapsar, Pune was clinically diagnosed as Karnasrava (Otitis externa) and pus culture positive for Klebsiella species. We started the treatment with Gandhak Rasayana-an Ayurvedic formulation of 250mg two tablets in the morning and evening with lukewarm water for 21 days. The outcome of the treatment was observed as a reduction in Karnashula (otalgia), Karnasrava (ear discharge), Karnakandu (itching), ear blockage and inflammatory changes. Post-treatment culture was negative for the organism. The improvement was noted in Brighton grading scale from grade III to grade I. Gandhak Rasayana showed significant antibacterial activity in the present case. Evaluating its antibacterial, antifungal and anti-inflammatory activity can provide scientific evidence for the study.

Ayurveda Rasayana Therapy (ART) leads to tumor regression and increased survival in chemo-intolerance high-grade stage IV follicular lymphoma: A case study.

Key clinical message: Ayurveda Rasayana Therapy (ART) may serve as a safe and effective alternative treatment option for chemo-intolerance high-grade stage IV follicular lymphoma patients for increasing survival and tumor regression. Abstract: Follicular lymphoma (FL), also called follicle center lymphoma/nodular lymphoma, observed in the B lymphocytes (B-cells). Available therapeutic options for follicular lymphoma are associated with various side effects and, patients with co-morbidities can seldom tolerate the chemotherapy regimens. Rasayana therapy not only resulted in tumor regression and improved survival but also dealt with the adverse effects of previous chemotherapy drugs. Herein, we present a case of a 74-year-old female diagnosed with Follicular lymphoma who had undergone three cycles of chemotherapy with unresolved disease outcome and serious adverse events. The patient refused to undergo further cycles of chemotherapy. Her family decided to start Ayurveda treatment for her as an alternative therapy for cancer care. On thorough case taking considering the Ayurveda parameters personalized Rasayana therapy as planned for the patient with an aim for improvement in Quality of Life (QoL), increasing survival, and optimizing body's immune response to fight the tumor. After treatment of 8 months, this case demonstrated partial tumor response as evidenced by PET-CT-scan. Quality of Life as evaluated using FACT-G was also seen improved besides significant improvement in physical performance status evaluated using ECOG. The patient showed a survival of 3.5 years after starting Ayurveda Rasayana Therapy (ART). Rasayana therapy was well tolerated by the patient. This case report indicates the potential role of ART as a therapeutic option in geriatric cancer patients who are not eligible for cytotoxic interventions. Case warrants further systematic investigation to evaluate the potential role of ART in the treatment of geriatric cancer patients.

Effects of two Ayurvedic formulations, Dhanwantaram Kashaya and Saraswatarishta on life history parameters and toxic aggregates in Drosophila models of Huntington's and Alzheimer's disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Ayurveda, the traditional healthcare system native to India, employs dosage forms containing multiple herbs in treating various clinical conditions. Dhanwantaram Kashaya (DK) and Saraswatarishta (SA) are two such formulations containing multiple herbs in varied proportions. Kashaya is a liquid decoction while Arishta is fermented liquid with permissible quantity of self-generated alcohol in it. Both the formulations have been reported to have clinical efficacy in age-related memory impairment. Other mental disorders having clinical presentations similar to psychoses are the other indications for these tested formulations. AIM OF THE STUDY: The present study was performed to evaluate the efficacy of two Rasayana formulations i.e., DK and SA, used by clinicians in different neurodegenerative conditions. We tested these formulations in Alzheimer's (AD) and Huntington's disease (HD) models of Drosophila melanogaster. MATERIALS AND METHOD: Initial experiments looking for life-history parameters in wild-type larvae were carried out in three sets with hundred larvae in each set. These parameters were also studied in diseased models in four sets with eighty larvae in each set. Aß plaques and polyQ aggregates were looked at with the help of immunostaining technique and images were captured using confocal microscopy. RESULTS: The results revealed that 0.25% concentration of both the formulations improve longevity in wild-type flies. Larval development and adult lifespan in Eye-GAL4>Aß42 (AD) and GMR-GAL4>127Q (HD) larvae/flies reared on 0.25% & 0.50% DK and 0.25% & 1.00% SA improved substantially. Reduced Aß plaques and polyQ aggregates indicate disease suppression. CONCLUSION: DK and SA enhanced longevity in Drosophila melanogaster. Suppression of disease aggregates suggests their potential utility in treating AD and HD. Further clinical and pharmaceutical studies are required to confirm these results, however, this is a workable model to test multi-herbal formulations of Ayurveda in the forms they are clinically used.

An Ayurveda approach in the management of avascular necrosis of bilateral hip joint-A case report.

Avascular necrosis (AVN) is the condition where an interruption of the sub-chondral blood supply leads to the death of cellular components of bones typically at the weight-bearing joints. Here we present a case of a 48 years old male patient suffering from AVN for the last two months. The patient had pain in bilateral hip joints which was gradually radiating to the bilateral thigh. The patient also felt difficulty in cross-legged, sitting, and squatting. The Ayurveda diagnosis of the case was established as Asthimajjagata-vata (∼disease due to vitiation of Vatadosha in bone and bone marrow tissues). Oral treatment was administred initially for eight months, followed by a course of Panchatikta-kshira basti (medicated enema enriched with milk) and Shalishastika panda swedana (a specific type of sudation with a poultice of rice bolus) for 24 days. Oral medications were continued during this duration and also for the subsequent 22 months. Kaishora guggulu in the dose of 750 mg twice a day with Dashamula kwath 40 ml twice a day, Ashwagandha churna (Powder of Withania somnifera Dunal) 3 g, Guduchi churna (Powder of Tinospora cordifolia L.) 1g, Chopchini churna (Powder of Smilax china L.) 2g and Shilajatwadi loha 500 mg with milk twice a day were advised to the patient. MRI scans of bilateral hip joints after 23 months of this treatment revealed changes in AVN grade, with the left hip joint transitioning from grade III-B to grade II, and the right hip joint progressing from grade IV-A to grade III. The range of motion at these joints was also improved significantly. Most of these medicines are Rasayana (∼immune-modulatory) in nature. The present case study suggests that Panchakarma procedures and Rasayana may be used for the treatment of AVN.

Mechanistic role and potential of Ayurvedic herbs as anti-aging therapies.

INTRODUCTION: Medicinal plants and herbs are the most important part of the Ayurveda. The term Rasayana in Charaka Samhita confers long life, youthfulness, strong body, freedom from diseases and the plants mentioned in Rsayana possess antiaging property. Aging is the collective term used for the complex detrimental physiological changes that reduce the functional ability of the cell. Oxidative stress, telomeres shortening, inflammation, and mitochondrial dysfunction are the main factors that regulate the aging process. Chronological aging is an irreversible process but the factors causing biological aging can be controlled. Ayurvedic herbs are better for the management of age-related problems. There are several natural bioactive agents present in plants that can delay the aging process in humans. They trigger actions like enhancing gene longevity and telomerase activity, ROS scavenging furthermore regeneration of tissues. CONTENT: The plants mentioned in the Rasayana of Ayurveda have antiaging potential and can be used to solve modern problems related to aging. Some Ayurvedic plants and their antiaging potential has explained in this review. The main causes of aging, medicinal plants and their use as potential antiaging mediator are covered in this study. SUMMARY: The process of aging is still an enigma. It is a complex, irretrievable, dynamic process that involves a number of factors and is subject to a number of environmental and genetic influences. Rasayana aspect has not been much investigated in clinical trials. Aging is considered to result from free radical damage. According to Charaka, Rasayana drugs open the partially or fully blocked channels. Many Rasayanas show free radical scavenging activity and has the potential to mitigate the effects of aging. It gives an overview of the significance of Ayurvedic medicinal plants as a source of inspiration and the use of these plants as remedies for antiaging. OUTLOOK: This study briefly outlooks the causes of aging and how medicinal plants can be used to reverse the aging process. In this study, we discussed the antiaging potential and mechanistic roles of Ayurvedic herbs. These herbs have the properties to slow down the natural process of aging and can successfully manage common age-related problems.

Mechanistic role and potential of Ayurvedic herbs as anti-aging therapies.

INTRODUCTION: Medicinal plants and herbs are the most important part of the Ayurveda. The term Rasayana in Charaka Samhita confers long life, youthfulness, strong body, freedom from diseases and the plants mentioned in Rsayana possess antiaging property. Aging is the collective term used for the complex detrimental physiological changes that reduce the functional ability of the cell. Oxidative stress, telomeres shortening, inflammation, and mitochondrial dysfunction are the main factors that regulate the aging process. Chronological aging is an irreversible process but the factors causing biological aging can be controlled. Ayurvedic herbs are better for the management of age-related problems. There are several natural bioactive agents present in plants that can delay the aging process in humans. They trigger actions like enhancing gene longevity and telomerase activity, ROS scavenging furthermore regeneration of tissues. CONTENT: The plants mentioned in the Rasayana of Ayurveda have antiaging potential and can be used to solve modern problems related to aging. Some Ayurvedic plants and their antiaging potential has explained in this review. The main causes of aging, medicinal plants and their use as potential antiaging mediator are covered in this study. SUMMARY: The process of aging is still an enigma. It is a complex, irretrievable, dynamic process that involves a number of factors and is subject to a number of environmental and genetic influences. Rasayana aspect has not been much investigated in clinical trials. Aging is considered to result from free radical damage. According to Charaka, Rasayana drugs open the partially or fully blocked channels. Many Rasayanas show free radical scavenging activity and has the potential to mitigate the effects of aging. It gives an overview of the significance of Ayurvedic medicinal plants as a source of inspiration and the use of these plants as remedies for antiaging. OUTLOOK: This study briefly outlooks the causes of aging and how medicinal plants can be used to reverse the aging process. In this study, we discussed the antiaging potential and mechanistic roles of Ayurvedic herbs. These herbs have the properties to slow down the natural process of aging and can successfully manage common age-related problems.

The clinical evaluation of Basti along with Rasayana on symptoms of post-COVID-19 syndrome: an open-labeled proof of concept pragmatic study-a study protocol.

BACKGROUND: Post-COVID-19 syndrome is a result of triggering various immune pathways and metabolic disturbances. Basti is an important per rectal Ayurveda-based treatment having multi-targeted actions. Basti and Rasayana treatment modulate immune responses by regulating pro-inflammatory cytokines, immune globulins, and functional properties of T cell. We propose to study the clinical evaluation of Basti along with Rasayana (rejuvenation therapy) on symptoms of post-COVID 19 syndrome. METHODS AND ANALYSIS: We designed a prospective, open-labeled proof of concept pragmatic study. The study duration is 18 months, and the intervention period are 35 days from the day of enrollment of the patients. The patients will be treated on the basis of Ayurvedic classification of Santarpanottha (over nutrition) symptoms and Apatarpanottha (lack of nutrition) symptoms. The Santarpanottha group will be treated within 3-5 days of oral Guggulu Tiktak Kashayam followed by 8 days of Yog Basti treatment and then 21 days of Rasayana therapy with Brahma Rasayan. The Apatarpanottha group will be treated within 3-5 days of oral Laghumalini Vasant, followed by 8 days of Yog Basti treatment and then 21 days of Kalyanak Ghrit. The outcome measures of this study will be to evaluate the changes in fatigue severity scale, MMRC dyspnea chest pain scale, pain score assessed by VAS scale, smell and taste scale, WOMAC scale, Hamilton depression scale, Hamilton anxiety scale, Insomnia Severity Index, change in Cough Severity Index, facial aging scale, dizziness scale, Pittsburgh Sleep Severity Quality Index, functional status scale, and heart palpitation scale. All adverse events will be monitored at each time throughout the study visit time. A total of 24 participants will be recruited to demonstrate with 95% confidence interval and 80% power. DISCUSSION: Ayurveda treats Santarpanottha (originated from over nutrition) symptoms and Apatarpanottha (symptoms originated from undernutrition) symptoms differently; hence, inspite of the same disease or symptom management, changes depend upon the type of the origin. This pragmatic clinical study is developed on the fundamental grounds of Ayurveda. ETHICS AND DISSEMINATION: Ethics approval was obtained through the Institutional Ethics Committees of Government Ayurved College and Hospital on 23 July 2021. TRIAL REGISTRATION: The trial is prospectively registered with the Clinical Trial Registry of India on 17 August 2021 [CTRI/2021/08/035732] after the Institutional Ethics Committee approval [GACN/PGS/Synopsis/800/2021 Date 23/7/2021].

Phytochemicals of Withania somnifera as a Future Promising Drug against SARS-CoV-2: Pharmacological Role, Molecular Mechanism, Molecular Docking Evaluation, and Efficient Delivery.

Coronavirus disease (COVID-19) has killed millions of people since first reported in Wuhan, China, in December 2019. Intriguingly, Withania somnifera (WS) has shown promising antiviral effects against numerous viral infections, including SARS-CoV and SARS-CoV-2, which are contributed by its phytochemicals. This review focused on the updated testing of therapeutic efficacy and associated molecular mechanisms of WS extracts and their phytochemicals against SARS-CoV-2 infection in preclinical and clinical studies with the aim to develop a long-term solution against COVID-19. It also deciphered the current use of the in silico molecular docking approach in developing potential inhibitors from WS targeting SARS-CoV-2 and host cell receptors that may aid the development of targeted therapy against SARS-CoV-2 ranging from prior to viral entry until acute respiratory distress syndrome (ARDS). This review also discussed nanoformulations or nanocarriers in achieving effective WS delivery to enhance its bioavailability and therapeutic efficacy, consequently preventing the emergence of drug resistance, and eventually therapeutic failure.

Identification of potential lead compounds against BACE1 through in-silico screening of phytochemicals of Medhya rasayana plants for Alzheimer's disease management.

Alzheimer's disease is a progressive and irreversible neurodegenerative disease that accounts for 70-80% of dementia in the elderly. According to recent clinical data, the incidence of the disease is exponentially increasing with age. Beta-site amyloid precursor protein cleaving enzyme1 (BACE1) is an important molecule involved in the pathogenesis of Alzheimer's disease due to its early role in the amyloid cascade. Cleavage of amyloid precursor protein by BACE1 is the rate-limiting step leading to the production and aggregation of amyloid-beta plaques. A number of natural products are being identified as non-competitive BACE1 inhibitors. In Ayurveda, Medhya rasayana is a group of medicinal herbs, specifically used for managing neurological disorders and is known to be effective in improving cognitivity and intellect. This study aimed to analyze the pharmacological activity of bio-active compounds in Medhya rasayana plants against BACE1, employing structure-based docking approach. 11 compounds out of 876 were identified as potential hits, based on docking scores, binding energies, and interactions with the critical residues of BACE1. Possible neurological activities of these compounds were predicted using PASS server. Out of the 11 compounds screened, two compounds, 'Convolidine' from the plant Convolvulus pleuricaulis Choisy and 'N-(4-hydroxybutyl) phthalimide' from Glycyrrhiza glabra satisfied the pharmacological parameters of Lipinski rule of filtering and ADMET prediction. The binding stability of these compounds against BACE1 was confirmed by molecular dynamic simulation and post dynamic MM/GBSA calculations. Detailed analysis of the interaction with the critical amino acids in the active site revealed the possible inhibitory potential of these compounds of medicinal plant origin against BACE1.

In vitro effect of Withania somnifera, AYUSH-64, and remdesivir on the activity of CYP-450 enzymes: Implications for possible herb-drug interactions in the management of COVID-19.

Ayurvedic medicines Withania somnifera Dunal (ashwagandha) and AYUSH-64 have been used for the prevention and management of COVID-19 in India. The present study explores the effect of Ashwagandha and AYUSH-64 on important human CYP enzymes (CYP3A4, CYP2C8, and CYP2D6) to assess their interaction with remdesivir, a drug used for COVID-19 management during the second wave. The study also implies possible herb-drug interactions as ashwagandha and AYUSH-64 are being used for managing various pathological conditions. Aqueous extracts of ashwagandha and AYUSH-64 were characterized using LC-MS/MS. A total of 11 and 24 phytoconstituents were identified putatively from ashwagandha and AYUSH-64 extracts, respectively. In addition, in silico studies revealed good ADME properties of most of the phytoconstituents of these herbal drugs and suggested that some of these might possess CYP-450 inhibitory activity. In vitro CYP-450 studies with human liver microsomes showed moderate inhibition of CYP3A4, 2C8, and 2D6 by remdesivir, while ashwagandha had no inhibitory effect alone or in combination with remdesivir. AYUSH-64 also exhibited a similar trend; however, a moderate inhibitory effect on CYP2C8 was noticed. Thus, ashwagandha seems to be safe to co-administer with the substrates of CYP3A4, CYP2C8, and CYP2D6. However, caution is warranted in prescribing AYUSH-64 along with CYP2C8 substrate drugs. Furthermore, preclinical and clinical PK studies would be helpful for their effective and safer use in the management of various ailments along with other drugs.

A randomised controlled trial to evaluate the effect of GandhakaRasayana rectal suppository in post operative pain management in ano-rectal disorders.

BACKGROUND: Poorly managed post-operative pain can lead to complications and prolonged rehabilitation. Pain Management after ano-rectal surgery becomes important as it could hamper day to day activities, disturb sleep, alter appetite and bowel evacuations and decrease the quality of life. According to Acharya Sushrutha, pain (Shoola) cannot be produced without Vata dosha and Shoola (pain) is inevitable after Shastra (surgical) Karma (procedure) for which Basti (enema) is usually the management of choice. Rectal suppositories are one such dosage form that are extensively used in post-operative pain management especially after ano-rectal surgery. MATERIALS AND METHOD: In the study, a total of 40 patients who fulfilled the inclusion criteria were randomly divided to two groups comprising of 20 patients each. Patients of Group A were treated with Gandhaka Rasayana rectal suppository and Group B were treated with Diclofenac Sodium rectal suppository for post-operative 5 days. RESULTS: The overall comparative results revealed a statistically significant improvement of 85% in Group A and 80.39% in Group B. Gandhaka Rasayana which is Tridoshashamaka, Vatamaya Nivaraka (ameliorates diseases caused by Vata dosha), Agnivardhaka (improves appetite and metabolism) and Shoolahara (reduces pain) attains micro particle size with 88 Bhavana (trituration) that can be readily absorbed by the rectal mucosa to exhibit the required therapeutic action. CONCLUSION: The Bhavana Dravya (medium of trituration) used in the preparation of Gandhaka Rasayana have proven analgesic, anti-inflammatory, anti-bacterial action and is also said to promote wound healing. The present study reveals that there is significant effect of Gandhaka Rasayana rectal suppositories in managing post-operative pain of ano-rectal disorders.

An Insight of Clinical Evidence of Ayurveda Interventions in the Management of COVID-19 Patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) was caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and patients with COVID-19 may be treated with traditional medicine like Ayurveda alone or in combination with standard allopathic treatment, as Ayurveda is one of the oldest traditional medicinal systems followed by millions around the world. METHODS: The literature was searched in databases such as LitCOVID, Google Scholar, Science Direct, EBSCO, Scopus, Web of Science, EMBASE, and reference lists to identify articles relevant to the use of Ayurvedic medicines in the management of COVID-19. RESULTS: Several clinical studies have determined the efficacy of Ayurvedic medicines and formulations in the management of patients with COVID-19. CONCLUSION: The Ayurvedic medicines and formulations with antiviral, antioxidant, anti-inflammatory, and immunomodulatory properties could be used along with standard allopathic medicines to assist in the earlier detection of virus, speedy recovery of patients with COVID-19, faster discharge from hospitals, and the prevention of further deterioration.