DPP-4 inhibition mediated antidiabetic potential of phytoconstituents of an aqueous fruit extract of Withania coagulans (Stocks) Dunal: in-silico, in-vitro and in-vivo assessments.

The DPP-4 inhibition is an interesting target for the development of antidiabetic agents which promotes the longevity of GPL-1(Glucagon-like peptide 1). The current study was intended to assess DPP-4(Dipeptidyl Peptidase-4) inhibition mediated antidiabetic effect of phytocompounds of an aqueous fruit extract of Withania coagulans (Stocks) Dunal by in-vitro, in-silico and in-vivo approaches. The phytoconstituents screening was executed by LCMS (Liquid Chromatography with tandem mass spectrometry). The in-vitro and in-vivo, DPP-4 assays were performed by using available kits. The in-vitro DPP-4 activity was inhibited up to 68.3% by the test extract. Accordingly, in-silico determinations of molecular docking, molecular dynamics and pharmacokinetics were performed between the target enzyme DPP-4 and leading phytocompounds. The molecular dynamics authenticated the molecular docking data by crucial parameters of cytosolic milieu by the potential energy, RSMD (Root Mean Square Deviation), RSMF (Root Mean Square Fluctuation), system density, NVT (Number of particles at fixed volume, ensemble) and NPT (Number of particles at fixed pressure, ensemble). Accordingly, ADMET predictions assessed the druggability profile. Subsequently, the course of the test extract and the sitagliptin (positive control), instigated significant (p ≤ 0.001) ameliorations in HOMA indices and the equal of antioxidants in nicotinamide-streptozotocin induced type 2 diabetic animal model. Compassionately, the histopathology represented increased pancreatic cellular mass which caused in restoration of histoarchitectures. It has been concluded that phytoconstituents in W. coagulans aqueous fruit extract can regulate DPP-4, resulting in improved glucose homeostasis and enhanced endocrinal pancreatic cellular mass.Communicated by Ramaswamy H. Sarma.

Ameliorations in dyslipidemia and atherosclerotic plaque by the inhibition of HMG-CoA reductase and antioxidant potential of phytoconstituents of an aqueous seed extract of Acacia senegal (L.) Willd in rabbits.

The assigned work was aimed to examine the capability of phytoconstituents of an aqueous seed extract of Acacia senegal (L.) Willd to inhibit HMG-CoA reductase and regression of the atherosclerotic plaque. The chemical fingerprinting of the test extract was assessed by LC-MS/MS. Consequently, the analyses of in-vitro, in-vivo, and in-silico were executed by using the standard protocols. The in-vitro assessment of the test extract revealed 74.1% inhibition of HMG-CoA reductase. In-vivo assessments of the test extract indicated that treated hypercholesterolemic rabbits exhibited a significant (P≤0.001) amelioration in the biomarker indices of the dyslipidaemia i.e., atherogenic index, Castelli risk index(I&II), atherogenic coefficient along with lipid profile. Subsequently, significant reductions were observed in the atherosclerotic plaque and antioxidant levels. The in-silico study of molecular docking shown interactions capabilities of the leading phytoconstituents of the test extract i.e., eicosanoic acid, linoleic acid, and flavan-3-ol with target protein of HMG-CoA reductase. The values of RSMF and potential energy of top docked complexes were show significant interactions. Accordingly, the free energy of solvation, interaction angle, radius of gyration and SASA were shown significant stabilities of top docked complex. The cumulative data of results indicate phytoconstituents of an aqueous seed extract of Acacia senegal have capabilities to inhibit the HMG-CoA reductase and improve the levels of antioxidants.

Astaxanthin: A super antioxidant from microalgae and its therapeutic potential.

Astaxanthin is a ketocarotenoid, super antioxidant molecule. It has higher antioxidant activity than a range of carotenoids, thus has applications in cosmetics, aquaculture, nutraceuticals, therapeutics, and pharmaceuticals. Naturally, it is derived from Haematococcus pluvialis via a one-stage process or two-stage process. Natural astaxanthin significantly reduces oxidative and free-radical stress as compared to synthetic astaxanthin. The present review summarizes all the aspects of astaxanthin, including its structure, chemistry, bioavailability, and current production technology. Also, this paper gives a detailed mechanism for the potential role of astaxanthin as nutraceuticals for cardiovascular disease prevention, skin protection, antidiabetic and anticancer, cosmetic ingredient, natural food colorant, and feed supplement in poultry and aquaculture. Astaxanthin is one of the high-valued microalgae products of the future. However, due to some risks involved or not having adequate research in terms of long-term consumption, it is still yet to be explored by food industries. Although the cost of naturally derived astaxanthin is high, it accounts for only a 1% share in total astaxanthin available in the global market. Therefore, scientists are looking for ways to cut down the cost of natural astaxanthin to be made available to consumers.

Assessment of Serum Minerals in Subclinical Hypothyroid and Overt Hypothyroid Patients.

Background Hypothyroidism, the commonest form of hormonal dysfunction, is due to thyroid hormone deficiency or its impaired activity. Homeostasis of the metabolism of minerals is regulated by thyroid hormones. If there is any disorder of the thyroid it will lead to disturbances of metabolism of minerals. Aim To study and compare serum calcium and serum phosphorus levels in patients of subclinical hypothyroidism and correlation of these parameters with thyroid-stimulating hormone (TSH) levels. Materials and methods This study included 70 patients with subclinical hypothyroidism, 70 patients with overt hypothyroidism, and 70 age- and sex-matched healthy controls. Thyroid profile (estimation of free triiodothyronine [FT3], free thyroxine [FT4], TSH) was done. In both cases and controls serum calcium and serum phosphorus levels were estimated. Results Serum calcium and phosphorus levels in patients of subclinical hypothyroidism was 8.75 ± 0.40 mg/dL and 3.80 ± 0.62 mg/dL, respectively. In patients with hypothyroidism it was 8.37 ± 0.52 mg/dL and 4.10 ± 0.75 mg/dL, respectively, and in controls it was 9.67 ± 0.97 mg/dL and 3.70 ± 0.71 mg/dL, respectively. Difference between these groups was statistically significant (p<0.05 ). Mean serum calcium and phosphorus for patients with TSH level <10 was 8.81 ± 0.33 mg/dL and 3.67 ± 0.60 mg/dL, respectively, and for TSH level >10 was 8.59 ± 0.51 mg/dL and 4.12 ± 0.54 mg/dL, respectively. The difference between both groups was statistically significant (p<0.05) for calcium, phosphorus . Conclusions In subclinical hypothyroidism serum calcium and serum phosphorus levels are significantly altered. Regular follow-up and estimating serum levels of these minerals in subclinical hypothyroidism patients should be done so it is beneficial to give mineral supplementations to prevent bone complications during the treatment of the disease.

Identification of phytochemicals as potential therapeutic agents that binds to Nsp15 protein target of coronavirus (SARS-CoV-2) that are capable of inhibiting virus replication.

BACKGROUND: Coronavirus disease 2019 (COVID-19) playing havoc across the globe caused 585,727 deaths and 13,616,593 confirmed cases so far as per World Health Organization data released till 17th July 2020. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) is responsible for causing this pandemic across different continents. It is not only impacting the world economy but also quarantined millions of people in their homes or hospitals. PURPOSE: At present, there is no Food and Drug Administration-approved drug or vaccine available to treat this disease. Still, people are trying various pre-existing medicines that are known to have anti-viral or anti-parasitic effects. In view of this, the present study aimed to study the binding potential of various phytochemicals present in multiple natural plant extract as a secondary metabolite to non-structural protein 15 (Nsp15) protein, a drug target known to play a crucial role in virulence of coronavirus. METHOD: Nsp15 protein was selected because it shows 89% similarity to the other SARS-CoV, which caused the earlier outbreak. The assumption is that inhibition of Nsp15 slowdowns the viral replication. Phytochemicals are selected as these are present in various plant parts (seed, flower, roots, etc.), which are used in different food cuisines in different geographical regions across the globe. The molecular docking approach was performed using two different software, i.e., Autodock, and Swissdock, to study the interaction of various phytochemicals with Nsp15 protein. Hydroxychloroquine is used as a positive control as it is used by medical professionals showing some positive effects in dealing with coronavirus. RESULTS: The present study demonstrated the binding potential of approximately 50 phytochemicals with Nsp15 and capable of inhibiting the viral replication, although in vitro and in vivo tests are required to confirm these findings. CONCLUSIONS: In conclusion, the present study successfully demonstrated the binding of phytochemicals such as sarsasapogenin, ursonic acid, curcumin, ajmalicine, novobiocin, silymarin and aranotin, piperine, gingerol, rosmarinic acid, and alpha terpinyl acetate to Nsp15 viral protein and they might play a key role in inhibiting SARS-CoV-2 replication.