Anti-oxidant potential of plants and probiotic spp. in alleviating oxidative stress induced by H2O2.

Cells produce reactive oxygen species (ROS) as a metabolic by-product. ROS molecules trigger oxidative stress as a feedback response that significantly initiates biological processes such as autophagy, apoptosis, and necrosis. Furthermore, extensive research has revealed that hydrogen peroxide (H2O2) is an important ROS entity and plays a crucial role in several physiological processes, including cell differentiation, cell signalling, and apoptosis. However, excessive production of H2O2 has been shown to disrupt biomolecules and cell organelles, leading to an inflammatory response and contributing to the development of health complications such as collagen deposition, aging, liver fibrosis, sepsis, ulcerative colitis, etc. Extracts of different plant species, phytochemicals, and Lactobacillus sp (probiotic) have been reported for their anti-oxidant potential. In this view, the researchers have gained significant interest in exploring the potential plants spp., their phytochemicals, and the potential of Lactobacillus sp. strains that exhibit anti-oxidant properties and health benefits. Thus, the current review focuses on comprehending the information related to the formation of H2O2, the factors influencing it, and their pathophysiology imposed on human health. Moreover, this review also discussed the anti-oxidant potential and role of different extract of plants, Lactobacillus sp. and their fermented products in curbing H2O2­induced oxidative stress in both in-vitro and in-vivo models via boosting the anti-oxidative activity, inhibiting of important enzyme release and downregulation of cytochrome c, cleaved caspases-3, - 8, and - 9 expression. In particular, this knowledge will assist R&D sections in biopharmaceutical and food industries in developing herbal medicine and probiotics-based or derived food products that can effectively alleviate oxidative stress issues induced by H2O2 generation.

Biogenic Preparation and Characterization of Silver Nanoparticles from Seed Kernel of Mangifera indica and Their Antibacterial Potential against Shigella spp.

Shigellosis is a serious foodborne diarrheal disease caused by the Shigella species. It is a critical global health issue. In developing countries, shigellosis causes most of the mortality in children below 5 years of age. Globally, around 165 million cases of diarrhea caused by Shigella are reported, which accounts for almost 1 million deaths, in which the majority are recorded in Third World nations. In this study, silver nanoparticles were synthesized using Mangifera indica kernel (MK-AgNPs) seed extracts. The biosynthesized M. indica silver nanoparticles (MK-AgNPs) were characterized using an array of spectroscopic and microscopic tools, such as UV-Vis, scanning electron microscopy, particle size analyzer, Fourier transform infrared spectroscopy, and X-ray diffractometer. The nanoparticles were spherical in shape and the average size was found to be 42.7 nm. The MK-AgNPs exhibited remarkable antibacterial activity against antibiotic-resistant clinical Shigella sp. The minimum inhibitory concentration (MIC) value of the MK-AgNPs was found to be 20 µg/mL against the multi-drug-resistant strain Shigella flexneri. The results clearly demonstrate that MK-AgNPs prepared using M. indica kernel seed extract exhibited significant bactericidal action against pathogenic Shigella species. The biosynthesized nanoparticles from mango kernel could possibly prove therapeutically useful and effective in combating the threat of shigellosis after careful investigation of its toxicity and in vivo efficacy.

Assessment of phytochemicals, antioxidants and in-silico molecular dynamic simulation of plant derived potential inhibitory activity of Thalictrum foliolosum DC. and Cordia dichotoma G. Forst. against jaundice.

Medicinal plants have been exploited for therapeutic purposes since the dawn of civilization and have long been acknowledged essential to human health. The purpose of this research is to examine the scientific evidence for using the therapeutic herbal plants Thalictrum foliolosum DC. and Cordia dichotoma G. Forst. to treat hepatitis illness. The fundamental explanation for the therapeutic relevance of these plants is phytochemicals, which were evaluated qualitatively and quantitatively in three separate extracts with different solvent properties (methanol-polar, chloroform-non-polar, and aqueous-polar as one of the bases of traditional use). Flavonoids, phenols, tannins, saponins, and alkaloids were all evaluated for their presence in plant extracts, and it was observed that methanolic extract had the highest content of phytochemicals among different extracts whereas, the aqueous extract showed least amount of phytochemicals. Additionally, the antioxidant activity of these plants was also evaluated and methanolic extract was revealed with potential antioxidant activity, as also evidenced by the lowest half inhibitory concentration (IC50) values in the DPPH, ABTS, and high %inhibition in µM Fe equivalent of FRAP assays. Following that, the dominant phytochemicals were investigated using ultra-high performance liquid chromatography from the selected plants. Furthermore, default docking algorithms were used to appraise the dominant phytoconstituents for their in-silico investigation, in which rutin was found with the highest binding affinity (8.2 kcal/mol) and interaction with receptor which is further involved in causing jaundice. The receptor is infact an enzyme that is sphingomyelin phosphodiesterase Leptospira interrogans (PDB: 5EBB) which is holded back in its position by rutin and do not interact with Leptospira inferrogans spp which causes jaundice. Overall, the study suggested that these herbs have significant therapeutic properties, and their in-silico analysis strongly recommends further clinical investigations to get insight into the mechanisms of action in curing variety of diseases.

Phytochemistry, and pharmacological efficacy of Cordia dichotoma G. Forst. (Lashuda): A therapeutic medicinal plant of Himachal Pradesh.

Cordia dichotoma, Indian cherry is one of the traditional medicinal plant well-known for its medicinal properties against variety of diseases primarily hepatocellular disorders. C. dichotoma is moderate size tree that may be found throughout the Himachal Pradesh and commonly called as lashuda. The objective of the present study is to emphasize the phytochemical and pharmacological study with hepatocurative assessment of C. dichotoma to strengthen not only traditional knowledge but also to validate scientific value of its medicinal potential. Furthermore, comprehensive literature information of C. dichotoma has been compiled from the variety of sources, including scientific databases like PubMed and Google Scholar and pertinent publications and books. The information provided in this study covers the years from 1956 to 2021 and KingDraw chemical structure editor software was used to depict the chemical structures of various secondary metabolites such as flavonoids, tannins, alkaloids, proteins carbohydrate and phenolic compounds extracted from the different parts of the C. dichotoma. Although, flavonoids and phenolic compounds are the most prominent phytoconstituents predominantly detected in C. dichotoma, which are known for great antioxidant potential and also they are renowned for their various pharmacological and therapeutic efficiency against various chronic diseases. Overall, the studies included in this review implies that the plant and its extracts have significant therapeutic benefits not only for hepatic but also for a variety of diseases. While further research is required to fully understand the processes underlying C. dichotoma application in various pharmacological activities.

Effects of a 2-Week 5000 IU versus 1000 IU Vitamin D3 Supplementation on Recovery of Symptoms in Patients with Mild to Moderate Covid-19: A Randomized Clinical Trial.

OBJECTIVE: Vitamin D deficiency has been associated with an increased risk of COVID-19 severity. This multi-center randomized clinical trial aims to determine the effects of 5000 IU versus 1000 IU daily oral vitamin D3 supplementation in the recovery of symptoms and other clinical parameters among mild to moderate COVID-19 patients with sub-optimal vitamin D status. STUDY DESIGN AND SETTING: A total of 69 reverse transcriptase polymerase chain reaction (RT-PCR) SARS-CoV-2 positive adults who were hospitalized for mild to moderate COVID-19 disease were allocated to receive once daily for 2 weeks either 5000 IU oral vitamin D3 (n = 36, 21 males; 15 females) or 1000 IU oral vitamin D3 (standard control) (n = 33, 13 males; 20 females). Anthropometrics were measured and blood samples were taken pre- and post-supplementation. Fasting blood glucose, lipids, serum 25(OH)D, and inflammatory markers were measured. COVID-19 symptoms were noted on admission and monitored until full recovery. RESULTS: Vitamin D supplementation for 2 weeks caused a significant increase in serum 25(OH)D levels in the 5000 IU group only (adjusted p = 0.003). Within-group comparisons also showed a significant decrease in BMI and IL-6 levels overtime in both groups (p-values < 0.05) but was not clinically significant in between-group comparisons. Kaplan-Meier survival analysis revealed that the 5000 IU group had a significantly shorter time to recovery (days) than the 1000 IU group in resolving cough, even after adjusting for age, sex, baseline BMI, and D-dimer (6.2 ± 0.8 versus 9.1 ± 0.8; p = 0.039), and ageusia (loss of taste) (11.4 ± 1.0 versus 16.9 ± 1.7; p = 0.035). CONCLUSION: A 5000 IU daily oral vitamin D3 supplementation for 2 weeks reduces the time to recovery for cough and gustatory sensory loss among patients with sub-optimal vitamin D status and mild to moderate COVID-19 symptoms. The use of 5000 IU vitamin D3 as an adjuvant therapy for COVID-19 patients with suboptimal vitamin D status, even for a short duration, is recommended.

Interference of quorum sensing regulated bacterial virulence factors and biofilms by Plumbago zeylanica extract.

There has been tremendous spread of antimicrobial resistance globally, mainly due to the excessive and unnecessary use of antibiotics, making the situation alarming. This has created a need for the development of alternative strategies to selectively target the bacterial pathogenicity without exerting selection pressure for the development of antimicrobial resistance. Targeting quorum sensing (QS)-mediated virulence and biofilms by nontoxic natural products is gaining importance as new control strategy to combat the virulence and biofilms of pathogenic bacteria. In this study, the crude extract of Plumbago zeylanica was fractioned in different solvents using liquid-liquid partitioning to obtain the most bioactive fraction. The inhibitory effect of the bioactive extract of P. zeylanica on QS at sub-minimum inhibitory concentrations (MICs) was studied against Chromobacterium violaceum 12472, Pseudomonas aeruginosa PAO1, and Serratia marcescens MTCC 97. Biofilm inhibition was studied using microtiter plate assay, scanning electron microscopy, and confocal laser scanning microscopy. Major phytocompounds detected were cinnamaldehyde dimethyl acetal, plumbagin, asarone, 4-chromanol, phthalic acid, palmitic acid, ergost-5-en-3-ol, stigmasterol, and ß-sitosterol. The violacein production in C. violaceum 12472 was reduced by >80% in the presence of P. zeylanica hexane fraction (PZHF; 200 µg/ml). The most active PZHF inhibited QS-mediated virulence factors of P. aeruginosa PAO1 such as pyocyanin, pyoverdin, rhamnolipid production, motility, etc., significantly at sub-MICs. Similarly, PZHF showed 59 to 76% inhibition of biofilm formation of above test pathogens. The findings revealed that active fraction of P. zeylanica was effective against the QS-regulated functions and biofilms development of Gram -ve pathogenic bacteria.

Vitamin D status of Arab Gulf residents screened for SARS-CoV-2 and its association with COVID-19 infection: a multi-centre case-control study.

OBJECTIVES: Vitamin D status in patients with COVID-19 is an on-going controversial issue. This study aims to determine differences in the serum 25(OH)D concentrations of Arab Gulf adult residents screened for SARS-CoV-2 and its association with risk of COVID-19 infection together with other comorbidities. METHODS: In this multi-center, case-control study, a total of 220 male and female adults presenting with none to mild symptoms were screened for COVID-19 (n = 138 RT-PCR-confirmed SARS-CoV-2 positive and 82 negative controls). Medical history was noted. Anthropometrics were measured and non-fasting blood samples were collected for the assessment of glucose, lipids, inflammatory markers and serum 25(OH)D concentrations. RESULTS: Serum 25(OH)D levels were significantly lower in the SARS-CoV-2 positive group compared to the negative group after adjustment for age and BMI (52.8 nmol/l ± 11.0 versus 64.5 nmol/l ± 11.1; p = 0.009). Being elderly (> 60 years) [Odds ratio 6 (95% Confidence Interval, CI 2-18; p = 0.001) as well as having type 2 diabetes (T2D) [OR 6 (95% CI 3-14); p < 0.001)] and low HDL cholesterol (HDL-c) [OR 6 (95% CI 3-14); p < 0.001)] were significant risk factors for COVID-19 infection independent of age, sex and obesity. CONCLUSIONS: Among Arab Gulf residents screened for SARS-CoV-2, serum 25(OH) D levels were observed to be lower in those who tested positive than negative individuals, but it was the presence of old age, diabetes mellitus and low-HDL-c that were significantly associated with risk of COVID-19 infection. Large population-based randomized controlled trials should be conducted to assess the protective effects of vitamin D supplementation against COVID-19.

Chemopreventive Effect of 5-Flurouracil Polymeric Hybrid PLGA-Lecithin Nanoparticles against Colon Dysplasia Model in Mice and Impact on p53 Apoptosis.

The use of 5-fluorouracil (5FU) is associated with multifaceted challenges and poor pharmacokinetics. Poly(lactic-co-glycolic acid)-lipid hybrid nanoparticles (PLNs)-based therapy has received attention as efficient carriers for a diversity of drugs. This study evaluated the in vivo chemotherapeutic and anti-proliferative efficacy of 5FU-loaded PLNs against 1,2-dimethylhydrazine (Di-MH) prompted colon dysplasia in mice compared to free 5FU. 5FU PLNs were prepared. Male Swiss albino mice were distributed to six experimental groups. Group 1: Saline group. All the other groups were injected weekly with Di-MH [20 mg/kg, s.c.]. Group 2: Di-MH induced colon dysplasia control group. Groups 3 and 4: Di-MH + free 5FU treated group [2.5 and 5 mg/kg]. Groups 5 and 6: Di-MH + 5FU-PLNs treated group [2.5 and 5 mg/kg]. Free 5FU and 5FU-PLNs doses were administered orally, twice weekly. Treatment with 5FU-PLNs induced a higher cytoprotective effect compared to free 5FU as indicated by lower mucosal histopathologic score and reduction in number of Ki-67 immunpositive proliferating nuclei. Additionally, there was significant upregulation of p53 and caspase 3 genes in colon specimens. Our results support the validity of utilizing the PLNs technique to improve the chemopreventive action of 5FU in treating colon cancer.

Protective effect of metformin on rat diabetic retinopathy involves suppression of toll-like receptor 4/nuclear factor-k B expression and glutamate excitotoxicity.

Microvascular complications of diabetes mellitus are progressively significant reasons for mortality. Metformin (MET) is considered as the first-line therapy for type 2 diabetes patients, and may be especially beneficial in cases of diabetic retinopathy although the precise mechanisms of MET action are not fully elucidated. The current study was designed to inspect the antioxidant and modulatory actions of MET on DRET in streptozotocin-induced diabetic rats. The effect of MET on the toll-like receptor 4/nuclear factor kappa B (TLR4/NFkB), inflammatory burden and glutamate excitotoxicity was assessed. Twenty-four male rats were assigned to four experimental groups: (1) Vehicle group, (2) Diabetic control: developed diabetes by injection of streptozotocin (60 mg/kg, i.p.). (3&4) Diabetic + MET group: diabetic rats were left for 9 weeks without treatment and then received oral MET 100 and 200 mg/kg for 6 weeks. Retinal samples were utilized in biochemical, histological, immunohistochemical and electron microscopic studies. MET administration significantly decreased retinal level of insulin growth factor and significantly suppressed the diabetic induced increase of malondialdehyde, glutamate, tumor necrosis factor-α and vascular endothelial growth factor (VEGF). Further, MET decreased the retinal mRNA expression of NFkB, tumor necrosis factor-α and TLR4 in diabetic rats. The current findings shed the light on MET's efficacy as an adjuvant therapy to hinder the development of diabetic retinopathy, at least partly, via inhibition of oxidative stress-induced NFkB/TLR4 pathway and suppression of glutamate excitotoxicity.