Bioactives of Hypericum perforatum to control diabetes: In vitro and in vivo biological evaluation in diabetic rats

Neelam Singh

Noida Institute of Engineering and Technology 19 Knowledge Park II, Institutional Area, Greater Noida 201306, UP, India

Background: Improving diabetes mellitus treatment is a significant contemporary medical and societal issue. Plant-based botanicals may lower blood sugar, enhance insulin absorption, and block important enzymes that contribute to the onset and course of diabetes. The preventive role of Hypericin perforatum and its constituent hypericin was studied using diabetic rats and in vitro cultures.

Methods: The in vitro glucose absorption by yeast cells, alpha-amylase, and glucosidase activity were used to examine the mechanism of action of Hypericum perforatum (HP) extract. The extract's safety and in vivo efficacy were studied using a Streptozotocin (STZ)-induced diabetic rat model. Hematology, blood biochemistry, and plasma insulin were also assessed.

Results: The extract significantly (p<0.03) enhanced the uptake of glucose through the plasma membrane of yeast along with α-amylase (p<0.05) and α-glucosidase (o.o4) inhibition activity in vitro. Meanwhile, the extract could significantly reduce renal (uric acid and creatinine), hepatic (SGOT, SGPT, and ALP), and lipid (triglycerides and cholesterol) profiles in the serum of diabetic rats. The extract was safe up to a 1000mg/kg dosage in preclinical acute dose toxicity studies. In diabetic rats, the extract reduced pancreatic histological alterations. This study found that the extract reduced STZ-induced diabetes and oxidative stress to liver and pancreatic tissue, as well as increasing plasma insulin levels in the treated rats.

Conclusion: Our findings indicate that Hypericum perforatum extract demonstrated protective activity by effectively halting the sequential progression of oxidative stress, renal and hepatic function test, lipid profile test, and STZ-induced histopathological alterations in the liver and pancreas.

Introduction: Kanchnar Guggulu (KG) is a potent Ayurvedic remedy for hormonal imbalances, PCOS, ulcers, cystic swelling, and tumors. PCOS is clinically significant, impacting one in five women during their reproductive years, leading to infertility, hyperandrogenism, and metabolic issues like insulin resistance and obesity. This study aims to explore KG's mechanism of action and investigate its potential therapeutic targets for PCOS.

Methodology: The formulation's phytochemicals were screened utilizing online databases such as IMPPAT, TCMSP, and literature mining. Subsequently, an ADME analysis was performed to screen the drug potential of the phytochemicals. Targets of the active ingredients were identified using databases like Similarity Ensemble Approach (SEA) and Swiss Target Prediction (STP). A transcriptomics analysis validated therapeutic targets, followed by gene ontology, pathway enrichment analyses, and PPI network establishment. Molecular docking was performed to visualize the interactions between the active molecules and network hub genes. The top three docked complexes were subjected to 250 ns MD simulation and GBMV analysis.

Results: The initial database-based screening identified 643 active ingredients, with 413 remaining post ADME analysis. Initially, 171 potential targets were identified from STP and SEA, of which 55 were differentially expressed in PCOS based on the transcriptome analysis. Top enriched pathways encompassed lipid and atherosclerosis, HIF-1 signaling, estrogen signaling, insulin signaling, etc. The toxicology-based screening process efficiently narrowed down a conclusive set of 83 bioactive molecules. These molecules were then subjected to computational docking with eight targets identified as hubs in the PPI analysis. The top three docked complexes identified were retinoic acid receptor (RAR)–curcumene, estrogen receptor (ESR)–shogaol, and platelet-activating factor receptor (PTAFR)–siphonodiol. Finally, the relative stability of the docked complexes was validated using MD simulation.

Conclusion: Our results not only validate the clinical efficacy of KG in treating PCOS but also establish a basis for subsequent experimental investigations.

The gel of low-esterification pectin has no special requirements for soluble solids and is often used as a thickening agent, gelling agent and stabilizer in food. Pectin is difficult to digest and absorb when ingested by the human body. It is mainly fermented and utilized by the intestinal flora at the end of the intestine to produce active substances such as short-chain fatty acids. Therefore, pectin may be able to regulate the composition of intestinal flora and affect human health. The intestinal flora is diverse, and there may be a preference for the utilization of low-ester pectin. This study selected three different human intestinal bacteria, including five strains of Bacteroides xylanolyticus, two strains of Enterococcus faecium and two strains of Bifidobacterium longum, to explore their differences in the degradation and utilization of low-esterification pectin. The culture medium was prepared using low-ester pectin L102 as the sole carbon source. Through the growth pattern, pH value, sugar content and short-chain fatty acid changes of each strain in the pectin culture medium, the degradation effect of the different intestinal bacteria on low-esterification pectin was elucidated. The results showed that Bifidobacterium longum had a weak ability to degrade low-ester pectin and poor growth. Both Bacteroides xylanolyticum and Enterococcus faecium can degrade low-esterification pectin and grow well, among which Bacteroides xylanolyticum Bt-17 and Enterococcus faecium ET-2 are the best. The difference is that Bacteroides xylanolyticum Bt-17 degrades low-esterification pectin to mainly produce acetic acid and propionic acid, while Enterococcus faecium ET-2 degrades low-esterification pectin to mainly produce acetic acid. The research results provide a theoretical basis for the selective interaction between low-ester pectin and the intestinal flora and provide a strategy for selectively regulating the composition of the intestinal flora.

Abstract

Stress is commonly known to induce various responses associated with psycho-somatic diseases, both on the general physical level and on a subtler molecular level. A growing interest has been seen in the use of yoga therapy to cope with stress. Though several control trials have shown a positive effect of yoga on stress, the extent to which adjuvant therapies like yoga may or may not have an effect on stress on the molecular level in the human body, as well as the mechanism involved in their potential efficacy, require further exploration.

Aim: To investigate the role of yoga in alleviating chromosomal translocations in security guards.

Methodology: The subjects' stress levels were evaluated using molecular parameters and Cohen’s Perceived Stress Scale, followed by an assessment of chromosomal translocations for t(14;18) and t(11;14) and an assessment of the DNA damage response and DNA repair through immunofluorescence and gene expression analysis.

Results and Conclusion: Yoga decreases cortisol levels among practitioners. It may also affect the DNA damage response and DNA repair.

Conflict of Interest: No conflicts of interest.

Need for this Study: This study may provide explanatory and exploratory ground for scientists in this field and help clinicians better understand the benefits of yoga as an adjunctive therapy for chronic diseases. This study may also provide research-based guidance for policy-makers internationally.

Numerous kinds of bioactive polysaccharides are identified as having intestinal immunomodulatory activity; however, the ways in which the different polysaccharides work differ. Therefore, we selected nine representative bioactive polysaccharides, including xanthan gum, inulin, guar gum, arabinogalactan, carrageenan, glucomannan, araboxylan, xylan, and fucoidan, and compared their intestinal immunomodulatory mechanisms. A cyclophosphamide (CTX)-induced immunosuppressed model was used in this experiment, the expression of CD4+ and CD8+ T cells in the ileum was detected by immunohistochemical staining, the relative expression levels of RORγt and T-bet in the ileum were determined by real-time quantitative PCR, the secretion of ileal cytokines TNF-α, IFN-γ, IL-17, and IL-22 was detected by ELISA kit, and the levels of SCFAs in the cecum contents were determined by gas chromatography, combined with UPLC-QTOF/MS for metabolomics analysis of colon contents, and 16S rRNA sequencing of gut microbes. The effects of these polysaccharides on the number of T cells in the intestinal mucosa, expression of transcription factors and inflammatory factors, intestinal metabolome and gut microbiota were compared and discussed. The results revealed that the nine polysaccharides promote intestinal immunity in different ways. In detail, guar gum, inulin and glucomannan better alleviated immune suppression in intestinal mucosal T cells. Inulin improved the intestinal microenvironment by significantly upregulating the abundance of Lactobacillus and Monoglobus and promoted short chain fatty acid (SCFA) production. Fucoidan and carrageenan promoted the colonization of the beneficial bacteria Rikenella and Roseburia. In addition, fucoidan, inulin and carrageenan inhibited the colonization of harmful bacteria Helicobacter, upregulated the abundance of Clostridia_UCG-014 and alleviated the accumulation of amino acids, bile acids and indoles in the large intestine. In conclusion, our study uncovered the different intestinal immunomodulatory mechanisms of the different polysaccharides and provided a guideline for the development of superior intestinal immunomodulatory polysaccharides.

Non-alcoholic fatty liver disease (NAFLD) is a common metabolic liver disease with a significant increase in incidence worldwide. The escalating prevalence of obesity and diabetes have been identified as key factors contributing to NAFLD. wolfberry polyphenols, recognised as natural polyphenols, exhibit potent lipid-lowering properties and show efficacy in modulating enterotype. The therapeutic potential of wolfberry polyphenols in ameliorating high-fat intestinal conditions holds promise for alleviating and preventing the progression of NAFLD. Our study demonstrates that wolfberry polyphenols effectively alleviate NAFLD-associated glucose intolerance and ameliorate liver damage as evidenced by histological examination using HE staining. After treatment with 200 mg/kg worfberry polyphenols, the inflammatory infiltration completely disappeared, fat droplets essentially disappeared and the tissue morphology closely resembled that of the control check group compared to the hight fat diet group. Wolfberry polyphenols have a pronounced effect on reducing hepatic triglycerides, total cholesterol (TC), low-density lipoprotein (LDL) and high-density lipoprotein (HDL). In addition, enzyme-linked immunosorbent assay analyses indicate that wolfberry polyphenols significantly reduce serum levels of the inflammatory factors TNF-α, IL-6 and IL-10. Non-targeted liver metabolomic analysis indicates that Lycium barbarum polyphenols modulate NAFLD liver health primarily through the regulation of methionine and tryptophan pathways. Furthermore, wolfberry polyphenols exhibit regulatory effects on the content of short-chain fatty acids in the intestinal flora. These findings provide a solid theoretical basis and suggest a promising avenue for future research into the use of wolfberry polyphenols in the management of NAFLD. The study suggests that these polyphenols could serve as an alternative intervention for NAFLD by modulating oxidative stress, inflammatory factors, gut microbiota and endogenous liver metabolism.

In recent years, increasing concern has emerged regarding the presence of unexpected contaminants, such as metals, in commonly consumed food items, posing potential threats to human well-being. Evaluating contaminant levels is crucial to ensuring the safe consumption of these items, as global efforts to control food contamination have intensified due to associated health risks. This study collected and analyzed a hundred sweet samples using flame atomic absorption spectrometry (FAAS) and inductively coupled plasma–optical emission spectrometry (ICP-OES) to investigate the distribution, correlation, and multivariate analysis of 13 metals (Mg, Ca, Mn, Fe, Co, Cu, Zn, Al, Cr, Ni, As, Cd, and Pb). The accuracy of the metal analysis was confirmed by assessing baking chocolate (SRM 2384). Metal concentrations were utilized to calculate the average daily intake (ADI), target hazard quotients (THQs), hazard indices (HIs), carcinogenic risk (CR), and cumulative carcinogenic risk (CCR). Results indicated that most sweet samples exceeded WHO/FAO-permitted levels for Mn, Co, Pb, Cr, and Cd. The estimated daily intake (EDI) of Ca (7.47E-02) and Cr (2.05E-03) ranked highest among essential and potentially toxic elements, respectively. Although THQ values were below the threshold (<1), several sweets exhibited HI values surpassing the threshold (>1), posing significant health hazards. Alarming CCR values in the range of 10^–4 were observed in many sweet samples, emphasizing the potential long-term health risks associated with their consumption. This study underscores the importance of monitoring essential and potentially toxic elements in wheat-based sweets and raises awareness about the associated health risks. These findings are critical for informing food safety regulations and promoting public health.

Background: Globally, 1% of all live births are affected by some form of congenital heart anomaly. Genetics and the environment both play a role in its causation, but very few of these aspects have been explored in the Indian subcontinent. One of the first and key transcription factors required for the formation of the heart during fetal development is NKX2-5. Several mutations in this gene have been identified for CHDs. In this study, we screened for known and novel variants to understand their role in CHDs.

Methods: Two exons and flanking 3’ and 5’ UTR regions of NKX2-5 were sequenced in n= 71 CHD cases, followed by a case–control test of association and a haplotype study.

Results: Only three known variants, namely rs2277923 (c.63A> G), rs3729753 (c.606G>C), and rs703752 (c.61G>T), were identified in a total of n= 69 cases. The case–control test of association revealed no significant allelic or haplotypic association. A genotypic association was observed for rs703752 in a recessive model (χ2 = 4.4702; p=0.03; risk score=0.33), along with a trend of association for rs3729753 (χ2 = 3.73; p=0.053; risk score=1.68) and rs703752 (p=0.082).

Discussion: Although we did not identify any new mutations in the coding regions of NKX2-5 gene, our findings are important observations for establishing an association between NKX2-5 variants and cardiac defects in the context of the north Indian population. There is a need to explore the roles of other transcription factors and cardiac developmental pathways and establish their interaction and role in disease biology in the Indian subcontinent.

Introduction: Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder that affects both children and adults and is characterized by persistent patterns of inattention, hyperactivity, and impulsivity. During adolescence, the prefrontal cortex develops connectivity with other brain regions to engage executive functions and impulsive behavior. Thus, injecting 6-hydroxydopamine, a neurotoxin, results in lesioning of dopaminergic neurons, which results in motor and cognitive impairments, similar to ADHD in humans. This study was planned to investigate the effect of agmatine, a primary amino compound and a member of guanidines, on 6-OHDA-induced ADHD-like behavior in mice. Methods: Animals administered with 6-OHDA on PND 5 exhibited the major ADHD-like symptoms, i.e. hyperactivity in an open-field test and attention deficit and impulsivity in an object-based attention task. Further, the model revealed discrete co-existing symptoms, i.e., memory deficits, anxiety-related compulsive-like behavior, and depressive and anti-social behavior, in a three-chamber social interaction task. Result: In the present study, 6-OHDA-induced ADHD-like behavior was significantly attenuated by agmatine (20, 40, and 80 mg/kg, i.p.), L-Arginine (60 mg/kg, i.p.), and aminoguanidine (50 mg/kg, i.p.). Additionally, agmatine reduces elevated oxidative stress parameters and improves the reduced dopamine level in the 6-OHDA mouse brain. Conclusion: These findings suggest that agmatine can be a potential therapeutic target for behavioral alteration associated with ADHD.

Suillus mediterraneensis is an ectomycorrhizal mushroom of two-needle pines. The purpose of the present study is to initially determine the morphological characterization of the species and, thereafter, the mycochemical investigation of the hydro-methanolic extract in order to identify the main chemical classes of their composition in terms of secondary metabolites using simple and rapidly recognized methods and techniques. This survey is being carried out in the coastal region of Ghazaouet within the wilaya of Tlemcen. The morphological determination of the mushroom is based on a range of macroscopic features, including the cap (by its shape, size, color, and surface or its cuticle), the hymenophore, the hymenium (tubes: their color, their shape, and the way they are attached), the stipe (thickness and shape), and the flesh. Furthermore, microscopic examination, either fresh or with reagents, especially Melzer's reagent, is needed to determine the shape, ornamentation, and size of the spores. The macro-chemical reaction of the different parts can be useful. This identification allows us to determine the species S. mediterraneensis, the family of Suillaceae, under Pinus halepensis with the presence of granules on the stipe. The results of the mycochemical screening carried out on the extract showed the presence of substances belonging to the classes of active compounds that include flavonoids, tannins, alkaloids, free quinones, reducing compounds, and coumarins. Anthraquinones, terpenoids, and saponins are absent. These preliminary results encourage the characterization of other molecules, and further studies are needed to evaluate their biological activities.