Impact of AYUSH 64 as an adjunctive to standard of care in mild COVID 19 - An open-label randomized controlled pilot study.

Background: Ayurveda herbal formulation AYUSH-64, proven to treat malaria and influenza-like illness in india was repurposed for COVID-19 patients considering preliminary evidances, however, scientific data was not available. Aim: To evaluate the preliminary efficacy and safety of AYUSH 64 as an add-on to standard of care in mild COVID19 patients. Materials and methods: A single centre, randomized, open-labeled, controlled, pilot study were conducted on mild COVID 19 confirmed patients. Patients allotted in interventional group (n = 41) recieved AYUSH 64, 3 gm per day in three divided dose for 14 days as an adjuvant to standard of care (SOC) whereas control group received SOC (n = 39) alone. Outcomes were reduction in WHO ordinal scale for clinical improvement, all-cause mortality, incidence of COVID19 symptoms among asymptomatic patients at baseline, use for oxygen therapy, use for a mechanical ventilator, the total duration of symptomatic phase and adverse events. Results: Mean score of WHO ordinal scale was reduced as time lapse in both the groups (f (1) = 20.5, p < 0.001) indicating clinical improvement among groups. There was no statistically significant difference in mean WHO ordinal scale between groups (f (1) = 0.98, p = 0.32). The proportion of asymptomatic patients progressing to the symptomatic stage is lower in AYUSH 64 group [OR, 0.68 (CI, 0.17-2.66)]. Mean days for the total duration of the symptomatic phase was also short in AYUSH 64 group (4.68 ± 3.29 days) compared to SOC group (5.81 ± 3.5 days). No incidence of the requirement of a mechanical ventilator, adverse drug reaction and death were observed in either of the groups. Conclusion: The findings of this pilot study show that an integrated approach of AYUSH 64 with SOC provide early trends of benefit by reduction in disease progression and in total symptom duration. However, its effects remains inconclusive on outcomes such as all cause mortality, use of oxygen therapy, invasive ventilator due to sparse outcomes.

Guduchi Ghanavati (Ayurveda medication) improves the perceived immunity in individuals at risk of SARS-CoV-2: A Multicentred, controlled, before-and-after study.

Introduction During the COVID-19 pandemic in India, Ayurvedic medication (Guduchi Ghanavati, GG) was prescribed by Ayurveda physicians for prevention and management. This study aimed to evaluate the prophylactic effect of GG in individuals with moderate to very high risk of SARS-CoV-2. Methods A multicenter, controlled, quasi-experimental, before-and-after study was conducted on individuals at moderate to very high risk of SARS-COV-2 exposure. In the intervention group (n = 15,992), participants received GG 1 g daily for 28 days in conjunction with standard preventive guidelines (SPG), while in the control group (n = 4953), participants were asked to follow SPG only. Outcomes were the incidence of COVID-19, perceived immune status, quality of life, and safety. The perceived immune status was assessed using a brief Likert-scale questionnaire having common immune-related complaints. Results Of the 20,945 enrolled, 20,574 completed the trial (intervention: 15,729, control: 4845). The percentage of participants who reported the incidence of COVID-19 was marginally lower in the GG+SPG group (41, 0.26%) than in the SPG group (16, 0.33%), leading to 21% (95% CI, -40% to 55%) efficacy of GG. However, the decrease in incidence percentage was statistically insignificant due to the trivial incidences reported. The scores of perceived immune status quality of life improved significantly from baseline in the GG+SPG group (p < 0.001) compared to the SPG group. Conclusion GG is safe and improves perception of immune status in individuals at risk of developing SRAS-CoV-2. However, these findings are inadequate to establish that GG lowers the incidence of COVID-19 necessitating to conduct RCTs in high-risk populations. Clinical Trial Registration CTRI/2020/06/025,525.

Add-on Ayurveda Treatment for Early Stage COVID-19: A Single Center Retrospective Cohort Study From Gujarat, India.

The retrospective cohort study aimed to evaluate the clinical outcomes of Ayurveda treatment exposure as an add-on to conventional care in early stage COVID-19 patients admitted at Samaras COVID care center, Ahmedabad, India. Conventional care included Vitamin-c, Azithromycin, and Paracetamol. Ayurveda formulations used as add-on were Dashamula and Pathyadi decoctions along with Trikatu powder, Sanshamani tablet, AYUSH-64 tablet AND Yastimadhu Ghana tablet for oral administration. Considering Add-on Ayurveda medicines as exposure of interest, patients who received Add-on Ayurveda medicines at least for 7 days were included in the exposed group while those who received only conventional care in unexposed group. Data was collected through record review and telephonic interviews. The outcomes of interest were the development of symptoms, duration of symptomatic phase in those progressing to symptomatic stage and mortality. Total 762 participants were included-[541 (71%) in the exposed group and 221 (29%) in the unexposed. Progression to symptomatic phase did not differ significantly between groups [27.6% in exposed, 24.6% in unexposed, adjusted RR 0.85; 95% CI 0.6-1.2]. The total duration of symptomatic phase among those progressing to the symptomatic stage was significantly decreased in the exposed group (x¯ = 3.66 ± 1.55 days in exposed (n = 133); x¯ = 5.34 ± 3.35 days in unexposed (n = 61), p < 0.001). No mortality was observed in either of the groups. Ayurveda Treatment as adjunctive to conventional care reduced the duration of symptomatic phase in early stage COVID-19 as compared to standalone conventional care. Add-on Ayurveda treatment has promising potential for management of early stage COVID-19.

Phytoplankton consortia as a blueprint for mutually beneficial eukaryote-bacteria ecosystems based on the biocoenosis of Botryococcus consortia.

Bacteria occupy all major ecosystems and maintain an intensive relationship to the eukaryotes, developing together into complex biomes (i.e., phycosphere and rhizosphere). Interactions between eukaryotes and bacteria range from cooperative to competitive, with the associated microorganisms affecting their host`s development, growth and health. Since the advent of non-culture dependent analytical techniques such as metagenome sequencing, consortia have been described at the phylogenetic level but rarely functionally. Multifaceted analysis of the microbial consortium of the ancient phytoplankton Botryococcus as an attractive model food web revealed that its all abundant bacterial members belong to a niche of biotin auxotrophs, essentially depending on the microalga. In addition, hydrocarbonoclastic bacteria without vitamin auxotrophies seem adversely to affect the algal cell morphology. Synthetic rearrangement of a minimal community consisting of an alga, a mutualistic and a parasitic bacteria underpins the model of a eukaryote that maintains its own mutualistic microbial community to control its surrounding biosphere. This model of coexistence, potentially useful for defense against invaders by a eukaryotic host could represent ecologically relevant interactions that cross species boundaries. Metabolic and system reconstruction is an opportunity to unravel the relationships within the consortia and provide a blueprint for the construction of mutually beneficial synthetic ecosystems.

Pharmacognostical evaluation of Psoralea corylifolia Linn. seed.

Psoralea corylifolia Linn. belonging to Fabaceae family is an important endangered plant that has been therapeutically used to treat different pathological manifestations since ages. It is commonly known as Bakuchi in Sanskrit. Though it is an important plant, till date, no pharmacognostical reports have been available on its seed. A lot of adulterations are also present in the market. The present study is aimed towards evaluating pharmacognostical and histochemical characteristics of the seeds of P.corylifolia Linn. in detail. Macroscopic and microscopic pharmacognostical characters of seeds and histochemical studies were noted by following standard methods. Pharmacognostical evaluation of seed shows the presence of volatile oil, silica deposits and stone cells. The observations found in current work can be considered as reference standards in future studies.

Metabolic survey of Botryococcus braunii: Impact of the physiological state on product formation.

The microalga Botryococcus braunii is widely regarded as a potential renewable and sustainable source for industrial applications because of its capability to produce large amounts of metabolically expensive (exo-) polysaccharides and lipids, notably hydrocarbons. A comprehensive and systematic metabolic characterization of the Botryococcus braunii race A strain CCAP 807/2 was conducted within the present study, including the detailed analysis of growth-associated and physiological parameters. In addition, the intracellular metabolome was profiled for the first time and showed growth- and product-specific fluctuations in response to the different availability of medium resources during the cultivation course. Among the identified metabolites, a constant expression of raffinose was observed for the first time under standard conditions, which has until now only been described for higher plants. Overall, the multilayered analysis during the cultivation of strain CCAP 807/2 allowed the differentiation of four distinct physiological growth phases and revealed differences in the production profiles and content of liquid hydrocarbons and carbohydrates with up to 84% of organic dry weight (oDW). In the process, an enhanced production of carbohydrates with up to 63% of oDW (1.36±0.03 g L-1) could be observed during the late linear growth phase, whereas the highest accumulation of extracellular hydrocarbons with up to 24% of oDW (0.66±0.12 g L-1) occurred mainly during the stationary growth phase. Altogether, the knowledge obtained is potentially useful for the general understanding of the overall physiology of Botryococcus braunii and provide important insights into the growth behavior and product formation of this microalga, and is thus relevant for large scale biofuel production and industrial applications.

Land-use and land-cover change in Western Ghats of India.

The Western Ghats (WG) of India, one of the hottest biodiversity hotspots in the world, has witnessed major land-use and land-cover (LULC) change in recent times. The present research was aimed at studying the patterns of LULC change in WG during 1985-1995-2005, understanding the major drivers that caused such change, and projecting the future (2025) spatial distribution of forest using coupled logistic regression and Markov model. The International Geosphere Biosphere Program (IGBP) classification scheme was mainly followed in LULC characterization and change analysis. The single-step Markov model was used to project the forest demand. The spatial allocation of such forest demand was based on the predicted probabilities derived through logistic regression model. The R statistical package was used to set the allocation rules. The projection model was selected based on Akaike information criterion (AIC) and area under receiver operating characteristic (ROC) curve. The actual and projected areas of forest in 2005 were compared before making projection for 2025. It was observed that forest degradation has reduced from 1985-1995 to 1995-2005. The study obtained important insights about the drivers and their impacts on LULC simulations. To the best of our knowledge, this is the first attempt where projection of future state of forest in entire WG is made based on decadal LULC and socio-economic datasets at the Taluka (sub-district) level.

Acute and subchronic toxicity study of Tamra Bhasma (incinerated copper) prepared with and without Amritikarana.

BACKGROUND: Tamra Bhasma (TB) is one among herbo-metallic preparations extensively used in routine ayurvedic practice. In the present era, Bhasma preparations used in ayurvedic system of medicines are always under stern observations for containing heavy metals which may raise the question of safety aspect. OBJECTIVE: In the present study, TB prepared with and without Amritikarana was subjected to toxicity study to ascertain the role of Amritikarana on safety profile of TB in rats. MATERIALS AND METHODS: Both the samples of TB were administered to rats for 28 consecutive days at the doses of 5.5, 27.5, and 55 mg/kg. The effects of both drugs were assessed on ponderal changes, hematological, serum biochemical, and histopathology of various organs. RESULTS: Results showed that both the samples of TB did not produce any sign and symptoms of toxicity at therapeutic dose level (5.5 mg/kg) and therapeutic equivalent dose (TED) × 5 (27.5 mg/kg) while at higher dose of TED × 10 (55 mg/kg) TB has mild toxicity in liver, kidney, heart, and thymus on repeated administration for 28 days in rats. The sample without Amritikarana has more magnitude of toxicity than the sample with Amritikarana. CONCLUSION: From the present study, it is concluded that TB with Amritikarana was found to be relatively safer than TB without Amritikarana at different dose levels in rats and hence suggest for safely use in humans at therapeutic dose level. It proves the role of Amritikarana in the preparation of TB.

Cardioprotective Activity of Pongamia pinnata in Streptozotocin-Nicotinamide Induced Diabetic Rats.

Pongamia pinnata (L.) Pierre has been used in traditional medicine for the treatment for diabetes and metabolic disorder. The aim of this study was to investigate the effect of petroleum ether extract of the stem bark of P. pinnata (known as PPSB-PEE) on cardiomyopathy in diabetic rats. Diabetes was induced in overnight fasted Sprague-Dawley rats by using injection of streptozotocin (55 mg/kg, i.p.). Nicotinamide (100 mg/kg, i.p.) was administered 20 min before administration of streptozotocin. Rats were divided into group I: nondiabetic, group II: diabetic control (tween 80, 2%; 10 mL/kg, p.o.) as vehicle, and group III: PPSB-PEE (100 mg/kg, p.o.). The blood glucose level, ECG, hemodynamic parameters, cardiotoxic and antioxidant biomarkers, and histology of heart were carried out after 4 months after STZ with nicotinamide injection. PPSB-PEE treatment improved the electrocardiographic, hemodynamic changes; LV contractile function; biological markers; oxidative stress parameters; and histological changes in STZ induced diabetic rats. PPSB-PEE (100 mg/kg, p.o.) decreased blood glucose level, improved electrocardiographic parameters (QRS, QT, and QTc intervals) and hemodynamic parameters (SBP, DBP, EDP, max dP/dt, contractility index, and heart rate), controlled levels of cardiac biomarkers (CK-MB, LDH, and AST), and improved oxidative stress (SOD, MDA, and GSH) in diabetic rats. PPSB-PEE is a promising remedy against cardiomyopathy in diabetic rats.

Fourier transform infrared analysis of Tamra Bhasma at different levels: A preliminary study.

INTRODUCTION: Tamra Bhasma, one among the herbo-metallic preparations is extensively used in Ayurveda for different conditions. To make it safe to use, Tamra has to pass through a set of classical pharmaceutical procedures including a series of quenching in prescribed liquids, followed by incineration with black sulfide of mercury and herbal juice of Citrus jambhiri Lush. and corm of Amorphophallus campanulatus Linn. FTIR profiles of Tamra Bhasma at different levels is not available. AIM: To evaluate the chemical changes in Tamra Bhasma at different steps by following Fourier transform infrared (FTIR) spectroscopy. MATERIALS AND METHODS: In current study, raw Tamra, intermediate samples obtained during purification, incineration and Amritikarana were analyzed using FTIR. RESULTS: It was observed that Shodhana procedure leads in the formation of bonds between surface particles of Tamra and Shodhana media. These formed bonds on the surface of Shodhita Tamra samples gave various sharp peaks representing presence of many functional groups. CONCLUSION: The FTIR spectra revealed that both Bhasma samples contained organic compounds probably in the form of a complex with common functional groups like alkyl, methyl, etc., which need further studies for exact characterization of the complexes.

Effect of tamra bhasma (calcined copper) on ponderal and biochemical parameters.

INTRODUCTION: Tamra Bhasma (TB) and its forms like Somnathi Tamra Bhasma (STB), etc., are in vogue since centuries in Ayurveda. The present study is carried out to evaluate the effect of TB and STB in different dose levels on ponderal and biochemical parameters in wistar strain albino rats to provide scientific basis for its safety profile. MATERIALS AND METHODS: TB and STB were prepared as per the classical guidelines and administered to wistar strain albino rats for 45 consecutive days. Blood was collected and rats were sacrificed on the 46(th) day. Ponderal and biochemical parameters were studied. RESULTS: Results showed significant decrease in serum cholesterol, High Density Lipoprotein (HDL) cholesterol, triglycerides, total protein, and serum alkaline phosphatase levels. Comparatively, all the differences in between the groups are insignificant and no pathological changes at ponderal and biochemical levels were observed. CONCLUSION: Based on these observations, it can be said that these formulations can be safely used in cases of hyperlipidemia.

L-glutamine supplementation prevents the development of experimental diabetic cardiomyopathy in streptozotocin-nicotinamide induced diabetic rats.

The objective of the present investigation was to evaluate the effect of L-glutamine on cardiac myopathy in streptozotocin-nicotinamide induced diabetic rats. Diabetes was induced in overnight fasted Sprague Dawely rats by using intraperitonial injection of streptozotocin (55 mg/kg). Nicotinamide (100 mg/kg, i.p.) was administered 20 min before administration of streptozotocin. Experimental rats were divided into Group I: non-diabetic control (distilled water; 10 ml/kg, p.o.), II: diabetic control (distilled water, 10 ml/kg, p.o.), III: L-glutamine (500 mg/kg, p.o.) and IV: L-glutamine (1000 mg/kg, p.o.). All groups were diabetic except group I. The plasma glucose level, body weight, electrocardiographic abnormalities, hemodynamic changes and left ventricular contractile function, biological markers of cardiotoxicity, antioxidant markers were determined after 4 months after STZ with nicotinamide injection. Histopathological changes of heart tissue were carried out by using H and E stain. L-glutamine treatment improved the electrocardiographic, hemodynamic changes; LV contractile function; biological markers; oxidative stress parameters and histological changes in STZ induced diabetic rats. Results from the present investigation demonstrated that L-glutamine has seemed a cardioprotective activity.

Pharmacognostical evaluation of Citrus jambhiri Lush. fruit.

BACKGROUND: Citrus jambhiri Lush., commonly known as Jambira Nimbu in Sanskrit is medium to large indigenous tree with spreading habit, less spiny than lemon and belonging to the family Rutaceae. In Ayurveda, it is used in many pharmaceutical procedures of purification (Sodhana), calcination (Marana) etc., Though it is an important plant, till date, no pharmacognostical reports have been available on its fruit. MATERIALS AND METHODS: Study of fruit and its powder, histochemical tests and preliminary physicochemical investigations were done. RESULTS AND CONCLUSION: Results showed prismatic crystals of calcium oxalate, aerenchyma cells, oil globules, pitted vessels, scalariform vessels, juicy sac, etc., Preliminary physicochemical analysis revealed loss on drying (1.1%), ash value (1.4%), alcohol soluble extract (28.6%), and water soluble extract (53.3%). These observations can be of use in future studies.

Assessment of genotoxic potential of hridayarnava rasa (a herbo-mineralo-metallic ayurvedic formulation) using chromosomal aberration and sperm abnormality assays.

OBJECTIVES: Herbo-mineral formulations are being successfully used in therapeutics since centuries. But recently, they came under the scanner for their metallic contents especially the presence of heavy metals. Hence it is the need of the hour to assess and establish the safety of these formulations through toxicity studies. In line with the various toxicity studies that are being carried out, Government of India expressed the need for conducting genotoxicity studies of different metal- or mineral-based drugs. Till date very few Ayurvedic herbo-mineral formulations have been studied for their genotoxic potential. The present study is aimed to evaluate the genotoxic potential of Hridayarnava Rasa. MATERIALS AND METHODS: It was prepared as per classical guidelines and administered to Swiss albino mice for 14 consecutive days. Chromosomal aberration and sperm abnormality assay were done to evaluate the genotoxic potential of the test drugs. Cyclophosphamide (CP) was taken as positive group and results were compared. RESULTS: All treated groups exhibited significant body weight gain in comparison to CP group. Results revealed no structural deformity in the above parameters in comparison to the CP-treated group. CONCLUSION: Reported data showed that both tested samples of Hridayarnava Rasa does not possess genotoxic potential under the experimental conditions and can be safely used.

Review of research works done on Tamra Bhasma [Incinerated Copper] at Institute for Post-Graduate Teaching and Research in Ayurveda, Jamnagar.

The metal, Tamra though mentioned in Ayurveda with a wide range of therapeutic utilities; is attributed with Ashta Maha Dosha. Hence, one should be cautious while using Tamra Bhasma. Considering the significance of Tamra in therapeutics, many studies have been carried out at different centers of India. Aim of the present study was to compile such available research works done on Tamra in the Department of Rasa Shastra and Bhaishajya Kalpana (RS and BK), IPGT and RA, Jamnagar and provide brief information about pharmaceutical, analytical, and pharmacological studies. Total eleven studies on Tamra Bhasma, which revalidated the impact of classical guidelines, safety issues, and therapeutic utilities, were screened from PG Department of RS and BK, Institute for Post-Graduate Teaching and Research in Ayurveda, Gujarat Ayurved University, Jamnagar. All studies revealed that Tamra Bhasma is safe clinically, experimentally at Therapeutic Equivalent Dose (TED) levels as no toxic hazards were reported during the treatment period. In all aspects (pharmaceutical, pharmacological, and clinical) Somnathi Tamra Bhasma has proven to be better than Tamra Bhasma. The clinical efficacy of Tamra Bhasma has been evaluated in Shvasa, Kasa, Yakrit Pliha Vriddhi, Grahani, etc. conditions. Satisfactory responses with a decrease in the intensity of signs and symptoms were reported in all the studies. Though certain limitations were observed in these researches, the results can be considered as a lead for further well stratified studies covering larger population. No adverse effects were reported in any of these studies.

Effect of concomitant administration of L-glutamine and cycloart-23-ene-3ß, 25-diol (B2) with sitagliptin in GLP-1 (7-36) amide secretion, biochemical and oxidative stress in streptozotocin - nicotinamide induced diabetic Sprague Dawley rats.

Previously we have reported that, cycloart-23-ene-3ß, 25-diol (called as B2) and L-glutamine stimulated glucagon like peptide-1 (GLP-1) (7-36) amide secretion diabetic rats. The objective of present investigation was to investigate the concomitant administration of cycloart-23-ene-3ß, 25-diol+sitagliptin and L-glutamine+sitagliptin in streptozotocin - nicotinamide induced diabetic Sprague Dawley. Type 2 diabetes was induced in overnight fasted male Sprague Dawley rats pre-treated with nicotinamide (100 mg/kg, i.p.) followed by administration of streptozotocin (55 mg/kg, i.p.) 20 min after. The rats were divided into; I- non-diabetic, II- diabetic control, III- Sitagliptin (5 mg/kg, p.o.)+cycloart-23-ene-3ß, 25-diol (1 mg/kg, p.o.), IV- Sitagliptin (5 mg/kg, p.o.)+L-glutamine (1000 mg/kg, p.o.). The concomitant treatment of cycloart-23-ene-3ß, 25-diol and L-glutamine with sitagliptin was 8 weeks. Plasma glucose, body weight, food and water intake were determined every week. Glycosylated haemoglobin, lipid profile, plasma and colonic active (GLP-1) (7-36) amide, plasma and pancreatic insulin, histology of pancreata and biomarkers of oxidative stress were measured after 8(th) week treatment. Concomitant administration of cycloart-23-ene-3ß, 25-diol and L-glutamine with sitagliptin significantly (p<0.001) reduced plasma glucose, glyoxylated haemoglobin, lipid profile and oxidative stress parameters compared to diabetic control groups. Both concomitant treatment increased plasma and pancreatic insulin as well as plasma and colonic active (GLP-1) (7-36) amide secretion. Histological analysis by Gomori staining observed less destruction of pancreatic ß cells. The result obtained from this study; it is concluded that concomitant administration of cycloart-23-ene-3ß, 25-diol+sitagliptin and L-glutamine+sitagliptin showed additive antihyperglycaemic effect in diabetic rats.

Biological and Medicinal Significance of Purines.

This article outlines the biological significance of one of the most important heterocycles, the purines. An attempt has been made to cover most of the physiologically as well as medicinally important compounds containing the purine derivatives. Purines are the drug molecules, which possess a variety of biological and medicinal significance.