Current Pharmaceutical Biotechnology - Online First

Metabolic syndrome encompasses conditions such as diabetes mellitus (DM), which has become increasingly prevalent. Chemically synthesized medications are commonly used to mitigate the effects of DM and its complications; however, these often result in undesirable side effects, including weight gain, digestive issues, and heart failure.

This review highlights the therapeutic potential of bioactive compounds and anti-diabetic plants that possess proven anti-diabetic properties. Focusing on phytomedicines also explores their possible mechanisms of action and positions this work relative to current reviews in the field.

A comprehensive literature analysis was conducted, emphasizing the therapeutic potential of bioactive compounds in anti-diabetic plants. Databases such as PubMed, Scopus, and Google Scholar were thoroughly searched to identify studies investigating the anti-diabetic properties and mechanisms of action of plant-derived bioactive compounds. Inclusion criteria focused on studies evaluating the pharmacological effects of herbal medicines, plant extracts, and isolated bioactive compounds on diabetes management.

Therapeutic plants, as sources of anti-diabetic compounds, offer significant advantages. They are affordable, exhibit minimal or no adverse effects, and do not necessitate strict dietary restrictions or intense exercise regimens. The integrated insights underscore the potential of phytomedicines to address limitations in current diabetes management strategies.

The unique focus on phytomedicines positions this review as a valuable resource for researchers and clinicians. Detailing mechanisms and evidence supporting the efficacy of these compounds, guides the development of innovative strategies for identifying and utilizing bioactive compounds in effective diabetes management.

Diet-related chronic diseases, such as cardiovascular diseases, obesity, diabetes, autoimmune diseases and cancer, are largely preventable with a healthy diet and lifestyle. Therefore, searching for dietary supplements rich in antioxidant and anti-inflammatory phytochemicals for the prevention and/or management of diet-related chronic diseases is an important strategy for controlling these diseases to reduce healthcare costs and sustain development.

The aim of the current research was to prepare dietary supplements from avocado fruit pulp [AFPDS] and evaluate their potential against various diet-related chronic diseases through in-vitro , in-vivo , and molecular docking studies.

Volatile compounds of avocado pulp were evaluated, and the total phenolic compounds, fatty acids, and phytosterols profiles of the AFPDS were determined.

D-limonene, methyl propanoate, isobutyl propanoate and pentanol were the principal volatile compounds in the avocado pulp. Total phenolic and flavonoids were present in the AFPDS by 9.65 mg GAE/g and 6.87 mg CE/g, respectively. Chlorogenic acid and cinnamic acid were the major and minor identified phenolic compounds in AFPDS, respectively. Oleic acid [75.06%] and β-Sitosterol [2.19%] were the highest fatty acid and phytosterol present in AFPDS, respectively. AFPDS recorded anti-inflammatory activity against nitric oxide [NO] production in RAW264.7 macrophages by 98.2µg/ml [IC50] and 164.8µg/ml [IC90]. AFPDS showed significant anti-inflammatory activity against carrageenan-induced rat paw edema. AFPDS showed antioxidant activity against DPPH and ABTS by 8.67 mg TE/g and 6.14 mg TE/g. AFPDS possessed anti-cancer activity against MCF7 and HPG2 at10.8µg/ml and 40.5µg/ml, respectively. AFPDS exhibited anti-diabetic activity as an inhibitor of α-amylase and α-glucosidase by26.35±0.77μg/ml and 0.55±0.163mg/ml, respectively. Molecular docking studies revealed high binding affinity of different active compounds present in AFPDS with cyclooxygenase-2, glutathione peroxidase, α-glucosidase and B-cell lymphoma-extra-large proteins.

AFPDS can be considered a new agent for the prevention and treatment of diet-related chronic diseases, such as diabetes and cancer, due to its anti-inflammatory, antioxidant, anticancer, and anti-diabetic activities, as demonstrated through in-vivo , in-vitro , and molecular docking studies.

Atherosclerosis (AS) is caused by the endothelium injury associated with oxidative stress. Previous studies have shown that the Phlegm-Eliminating and Stasis-Transforming Decoction (Huayu Qutan Decoction, HYQTD) has mitochondrial protective function. The objective of this research was to explore how HYQTD drug-containing serum (HYQTD-DS) could potentially protect mitochondrial energy production in endothelial cells (ECs) from injury caused by hydrogen peroxide (H2O2)-induced oxidative damage in AS through SIRT1/PGC-1α/ Nrf2 pathway.

After preparation of containing serum, the cells were divided into various categories, such as control group, H2O2 group (an oxidative damage model), HYQTD group, Selisistat (EX527, a SIRT1 inhibitor) combined with H2O2 group, and EX527 combined with HYQTD group. The evaluation of oxidative stress involved measuring reactive oxygen species (ROS) and malondialdehyde (MDA) generation, as well as Superoxide Dismutase (SOD) activity. Mitochondrial function and ultrastructure were measured by Transmission electron microscopy (TEM), mitochondrial membrane potential (MMP), rate of oxygen consumption (OCR), respiratory chain complex activities, and ATP production. The key proteins and gene levels in the SIRT1/PGC-1α/Nrf2 pathway was quantified by quantitative real-time PCR (RT-PCR) and Western blotting analysis.

We found oxidative stress, mitochondrial damage, and mitochondrial energy disorder in H2O2-induced ECs. However it indicated a marked reversal after pretreated with HYQTD-DS. Mechanistically, EX527 induced increased oxidative stress, worse mitochondrial dysfunction, and less ATP synthesis.

We demonstrated that HYQTD-DS attenuated oxidative stress, improved mitochondrial function, and up-regulated mitochondrial ATP synthesis by activating SIRT1/PGC-1α/Nrf2 pathway-induced mitochondrial biogenesis and its downstream NADH dehydrogenase (ubiquinone) flavoprotein 2 (NDV2).

This study evaluated the renoprotective effects of p-Coumaric acid nanoparticles (PCNPs) in nephropathic rats.

Six groups of male Albino Wistar rats were randomly assigned. Group 1 was the control, while Group 2 received 45 mg/kg of streptozotocin (STZ) to induce diabetic nephropathy. Groups 3, 4, and 5 received STZ (45 mg/kg) along with PCNPs at doses of 20, 40, and 80 mg/kg, respectively. Group 6 received 80 mg/kg of PCNPs without STZ. Body weight, blood glucose, insulin, hemoglobin (Hb), and glycosylated hemoglobin (HbA1c) levels were measured. Blood urea, serum creatinine, kidney antioxidant enzymes, and lipid peroxidation levels were also analyzed. Histological and immunohistochemical studies of kidney tissues were performed.

PCNPs (80 mg/kg) significantly reduced serum glucose, creatinine, and urea levels while increasing insulin levels and antioxidant activity in the kidneys. Histological analysis revealed that nephropathic rats exhibited cellular damage, including shrinkage of Bowman’s capsule and lesions in the kidneys, along with degeneration in the Islets of Langerhans in the pancreas. PCNPs treatment restored these morphological alterations in the pancreas, liver, and kidneys to near-normal. Furthermore, nephropathic rats had elevated IL-6 and TNF-α expression in the renal tubules and glomeruli, which was reduced following PCNPs treatment.

The findings suggest that PCNPs exhibit antihyperglycemic, antioxidant, anti-glycation, and renoprotective effects in STZ-induced diabetic nephropathy.

Prostate cancer is an androgen-dependent malignancy, and the use of androgen deprivation therapies frequently results in treatment resistance, relapse, and the development of aggressive castration-resistant tumors. Patchouli alcohol, a tricyclic sesquiterpene derived from Pogostemon cablin of the Labiatae family, has demonstrated potential in modulating inflammatory responses and tumor progression. This study aimed to investigate the mechanisms through which patchouli alcohol influences inflammatory pathways associated with prostate cancer using bioinformatics and experimental validation.

Differentially Expressed Genes (DEGs) were identified from the GSE46602 dataset, containing 36 prostate cancer and 14 normal prostate biopsy samples, using the GEO2R tool (adjusted P < 0.05). Functional annotation was performed using GO and KEGG databases, while PPI networks were constructed via STRING and Cytoscape. Key hub genes were identified. To validate the bioinformatics findings, qPCR and Western blotting were employed to confirm the differential expression of selected hub genes in DU145 prostate cancer cells treated with patchouli oil.

Bioinformatic analysis revealed 71 DEGs, including 35 upregulated and 36 downregulated genes. Thirteen hub genes were identified (DCK, APRT, ADK, KCNK9, ADSL, PKM, KCNK3, S100A10, ENTPD2, PKLR, ARHGEF38, TPK1, and AK5), which were enriched in pathways, such as MAPK, PI3K-Akt, Ras, and Rap1. Experimental validation confirmed the upregulation of DCK, APRT, KCNK9, ADSL, PKM, S100A10, ENTPD2, PKLR, ARHGEF38, and AK5, and the downregulation of ADK, KCNK3, and TPK1 at both the mRNA and protein levels.

Patchouli alcohol appears to influence multiple hub genes associated with prostate cancer progression through its modulation of key cellular signaling and metabolic pathways. These findings support its potential role as a therapeutic agent for prostate cancer.

This study aimed to comprehensively investigate the molecular landscape of gastric cancer (GC) by integrating various bioinformatics tools and experimental validations.

GSE79973 dataset, limma package, STRING, UALCAN, GEPIA, OncoDB, cBioPortal, DAVID, TISIDB, Gene Set Cancer Analysis (GSCA), tissue samples, RT-qPCR, and cell proliferation assay were employed in this study.

Analysis of the GSE79973 dataset identified 300 differentially expressed genes (DEGs), from which COL1A1, COL1A2, CHN1, and FN1 emerged as pivotal hub genes using protein-protein interaction network analysis. Subsequent validation across The Cancer Genome Atlas (TCGA) datasets confirmed their up-regulation in GC tissues compared to normal controls. Promoter methylation analysis revealed decreased methylation levels of these hubs in GC tissues, suggesting their potential role in tumorigenesis. Mutational analysis using cBioPortal showcased frequent mutations in these genes, particularly FN1, further highlighting their significance in GC pathogenesis. Survival analysis indicated their correlation with reduced overall survival rates among GC patients, supported by the development of a robust prognostic model. Prediction of hub-associated miRNAs and gene enrichment analysis provided insights into their regulatory mechanisms and downstream pathways, implicating their involvement in extracellular matrix remodeling and cell migration. Drug sensitivity analysis revealed correlations between hub gene expression and drug response, while RT-qPCR validation confirmed their up-regulation in clinical GC samples. Finally, functional assays demonstrated the impact of FN1 knockdown on cellular proliferation, colony formation, and wound healing capacities.

Overall, this study elucidates the crucial role of COL1A1, COL1A2, CHN1, and FN1 in GC pathogenesis and underscores their potential as diagnostic markers and therapeutic targets.