Analysis of Clinical Trial Registry of India for Evidence of Anti-Arthritic Properties of Withania somnifera (Ashwagandha).

BACKGROUND: Withania somnifera (Ashwagandha) is an herb with anti-inflammatory properties used in managing arthritis. There is significant clinical data in the public domain on the effects of Ashwagandha and this study was aimed at compiling and analysing these data in a structured manner. The major sources of evidence data were clinical trials and systematic review of extant literature. METHODOLOGY: Retrospective database search was conducted in the Clinical Trial Registry of India for trials registered from April 2008 to March 2020, and published literature related to the anti-arthritic effects of Withania somnifera were reviewed. RESULTS: In all, 77 registered clinical trials were analysed and common among them were interventional, single-centre, randomized, double-blind, two-arm studies with Placebo being the comparator. Similar findings were observed in the 10 published clinical trials on arthritis evaluated for this study. While industry- and government-sponsored trials were identified, government funded sites with approvals from Institutional Ethics Committees were preferred. Most trials were registered as Phase 2 with the highest number of sites in the state of Maharashtra. The solid dosage form was most preferred. CONCLUSION: While the effects of Withania somnifera on various disorders are being investigated by several clinical trials, the ones evaluated for this study provide insight on its potential in managing arthritis when given for a specific duration. Evidence shows a dosage of 6 gm in powder form or extracts in tablets, or 500 -1000 mg capsule consumed for a duration of 8 - 12 weeks may be useful in managing symptoms of arthritis in patients.

Mucormycosis: A triple burden in patients with diabetes during COVID-19 Pandemic.

With the upsurge in the cases of COVID-19 around the world, plenty of potential COVID-19 complications are becoming more prevalent, including a higher risk of secondary bacterial and fungal infections. Mucormycosis is one such condition which has high prevalence among individuals with diabetes who were infected with COVID-19.The usage of steroids in the treatment further inflates the risk of infection and exacerbation of disease in pre-existent mucormycosis patients. Generally, Corticosteroid-induced diabetes can arise on long-term steroid medication, increasing the likelihood of mucormycosis. In patients with COVID-19, the indications and dose of corticosteroids should be properly regulated, and persons with diabetes who take insulin or oral anti-diabetic medicines should be cautious. To avoid poor outcomes, strategies to improve glycemic management should be emphasized. This narrative review elucidates different disciplines on rampant use of steroids, iron and zinc supplements as well as the methods utilized as primary or adjunctive treatment of this fatal condition. This article may help to pave the way for robust research that needs to be done to tackle the deadly triple burden of the disease.

A review on treatment of petroleum refinery and petrochemical plant wastewater: A special emphasis on constructed wetlands.

Petroleum refinery and petrochemical plants (PRPP) are one of the major contributors to toxic and recalcitrant organic polluted water, which has become a significant concern in the field of environmental engineering. Several contaminants of PRPP wastewater are genotoxic, phytotoxic, and carcinogenic, thereby imposing detrimental effects on the environment. Many biological processes were able to achieve chemical oxygen demand (COD) removal ranging from 60% to 90%, and their retention time usually ranged from 10 to 100 days. These methods were not efficient in removing the petroleum hydrocarbons present in PRPP wastewater and produced a significant amount of oily sludge. Advanced oxidation processes achieved the same COD removal efficiency in a few hours and were able to break down recalcitrant organic compounds. However, the associated high cost is a significant drawback concerning PRPP wastewater treatment. In this context, constructed wetlands (CWs) could effectively remove the recalcitrant organic fraction of the wastewater because of the various inherent mechanisms involved, such as phytodegradation, rhizofiltration, microbial degradation, sorption, etc. In this review, we found that CWs were efficient in handling large quantities of high strength PRPP wastewater exhibiting average COD removal of around 80%. Horizontal subsurface flow CWs exhibited better performance than the free surface and floating CWs. These systems could also effectively remove heavy oil and recalcitrant organic compounds, with an average removal efficiency exceeding 80% and 90%, respectively. Furthermore, modifications by varying the aeration system, purposeful hybridization, and identifying the suitable substrate led to the enhanced performance of the systems.

Phytochemicals As Uropathognic Escherichia Coli FimH Antagonist: In Vitro And In Silico Approach.

BACKGROUND: Urinary tract infection (UTI) is caused by uropathogenic Escherichia coli (UPEC). The UPEC initiate pathogenesis by expressing type 1 pili, which attach to membrane receptors on the uroepithelial cells. Inhibition of attachment can provide a valuable target for prophylaxis in symptom-free milieu. METHODS: The antibacterial efficacy of alcoholic, hydroalcoholic and aqueous extracts of four plants namely Achyranthes aspera, Andrographis paniculata, Artemissia vulgaris and Glycyrrhiza glabra was evaluated against seven isolated bacterial strains and procured E. coli (UTI89/UPEC) strain. Screening of isolated strains was based on morphological characteristics and biofilm forming ability followed by physiological and biochemical analysis. RESULTS: The hydroalcoholic extracts of G. glabra at 50 µg/ml showed an impending antioxidant (DPPH) effect of 95.65% compared to ascorbic acid. The MIC values of all the plant extracts against selected bacterial strains ranged between 125 to 1000 µg/ml. In silico molecular docking performed to make out the antiadhesive role of 115 documented phytochemicals from selected plants identified quercetin-3-glucoside, ethyl caffeate, liquiritoside, liquiritin and isoliquiritigenin as potential phytochemicals. Molecular dynamics simulation performed by PTRAJ module of Amber11 package to monitor the stability of hydrogen bond showed that quercetin-3-glucoside and ethyl caffeate are potential phytochemicals as antiadhesive forming H-bonds with the FimH protein ligand. CONCLUSIONS: Aforesaid phytochemicals demonstrate effective antibacterial activity through the anti-adhesion mechanism.

Rare association of congenital penile urethrocutaneous fistula with Y-type urethral duplication.

A 24-year-old man presented with symptoms of difficulty in passage of urine, mixed with gas and stool from penoscrotal junction since birth. He had a history of surgery (posterior sagittal anorectoplasty) for imperforate anus in first week of his life. On physical examination, external meatus was adequate with small 5×5 mm fistulous opening noted at penoscrotal junction with normal anal tone and opening. On evaluation with retrograde urethrography, voiding cystourethrogram, cystoscopy and barium enema, he was found to have penile urethrocutaneous fistula of 0.5×0.5 cm with Y-type incomplete urethral duplication. Urethroanal fistula (Y-type urethral duplication) was of small size (<5 mm), so closed primarily through perineal route with interposition of ischiorectal fat. Penile urethrocutaneous fistula (4 mm) too was closed primarily and covered with tunica vaginalis flap in single sitting. It has been 6 months since surgery and the patient is fully continent and voiding well with no urinary or faecal leak.

In vivo and in silico investigation of antidiabetic activity of fruit of withania coagulans Dunal.

This study evaluates the antidiabetic activities of methanolic extract of Withania coagulans Dunal (Ashutosh booti) fruit (WCFE) in poloxamer-407 induced type 2 diabetic Wistar rats. The electrochemical behaviour of WCFE with anodic peak of 1.19± 0.01V was found similar to standards used indicating that extract is antioxidant in nature. Unlike diabetic control rats, the WCFE treated diabetic rats presented significant amelioration of glycaemia, insulinamia and lipid dysmetabolism, remarkable reduction of oxidative markers and improved cecal and pancreatic characteristics. HYBRID and FRED docking were performed for 25 documented WCFE botanicals for putative action mechanism concerning three diabetic therapeutic proteins namely PTP-1B, PPAR-γ and DPP-IV fully support the in vivo findings. Botanicals like nicandrenone10 and Acnistin F have shown considerable interaction potential with aforesaid proteins. Results provide pharmacological evidence of WCFE as antihyperglyceamic mediated by interaction of various botanicals with various targets operating in diabetes mellitus.

Tocopherol from seeds of Cucurbita pepo against diabetes: validation by in vivo experiments supported by computational docking.

BACKGROUND/PURPOSE: Tocopherol from raw pumpkin seeds has been reported to be effective in the alleviation of diabetes through its antioxidant activities. This study evaluates the antidiabetic activities of the tocopherol fraction of raw seeds of Cucurbita pepo L. (CPSE) in a diabetic rat model. In addition, the putative action mechanisms of its botanicals were computationally investigated. METHODS: Seed water activity (Aw) was assessed. Tocopherol was extracted and quantified from raw seed oil. The effect of CPSE was studied in poloxamer-407 (PX-407)-induced type 2 diabetic Wistar rats. Glycemic, insulinemic, and lipid profiles, as well as lipid peroxidation status, were evaluated. Glucagon like peptide-1 (GLP-1) content in the cecum was evaluated and histopathological analysis of the pancreas was performed. Further, HYBRID and FRED docking were performed for 10 documented CPSE botanicals, for putative action mechanisms concerning three proteins [protein-tyrosine phosphatase 1B (PTP-1B), peroxisome proliferator-activated receptor gamma (PPAR-γ), and dipeptidyl peptidase IV (DPP-IV)] known to have diabetic therapeutic potential. RESULTS: The Aw of raw seeds was found to be 0.544 ± 0.002. Using tocopherol standards, HPLC determination of CPSE revealed the presence of tocopherol isomers (α, ß, γ, and δ). The tocopherol content was found to be 107.4 ± 2.9 mg/100 g of CPSE. When compared to diabetic control (DC) rats, the CPSE-treated diabetic rats presented a significant amelioration of glycemia, insulinemia, and lipid dysmetabolism. A remarkable reduction in oxidative markers and improved cecal and pancreatic characteristics were also observed. Tocopherol isomers have shown a considerable interaction potential with the aforesaid proteins in docking. CONCLUSION: The results provide pharmacological evidence of CPSE as an antihyperglycemic mediated by the interaction of various botanicals with multiple targets operating in diabetes mellitus (DM).

Antihyperglycemic activity with DPP-IV inhibition of alkaloids from seed extract of Castanospermum australe: Investigation by experimental validation and molecular docking.

The antidiabetic actions of Castanospermum australe Cunn., seed (CAS) extract were evaluated in Poloxamer-407 (PX-407) induced T2DM rats. The CAS extract (100 and 150 mg/kg body weight) was administered orally once a day for 5 weeks after the animals were confirmed diabetic. A significant increase in blood glucose, HbA1c and serum insulin levels were observed in T2DM rats in comparison to citrate control rats. Treatment with CAS extract in T2DM rats reduced the elevated levels of blood glucose, HbA1c and insulin with significant (p≤0.001) improvement in OGT. The CAS extract treatment also increased (p≤0.001) the K(ITT) and prevented increase in HOMA-R level in T2DM rats. The DPP-IV inhibitory potential of CAS extract showed IC50 value of 13.96 µg/ml whilst the standard Diprotin A displayed the IC50 value of 1.543 µg/ml. Molecular docking of the three reported alkaloids from the seeds of C. australe showed comparable DPP-IV inhibition with berberine. Our data suggest that CAS extract (150 mg/kg body weight) normalizes hyperglycemia in T2DM rats with strong DPP-IV inhibitory potential. The molecular docking showed that among the three alkaloids of seed extract 7-Deoxy-6-epi-castanospermine is a potent DPP-IV inhibitor similar to berberine.