Annona squamosa Fruit Extract Ameliorates Lead Acetate-Induced Testicular Injury by Modulating JAK-1/STAT-3/SOCS-1 Signaling in Male Rats.

Lead (Pb) is a common pollutant that is not biodegradable and gravely endangers the environment and human health. Annona squamosa fruit has a wide range of medicinal uses owing to its phytochemical constituents. This study evaluated the effect of treatment with A. squamosa fruit extract (ASFE) on testicular toxicity induced in male rats by lead acetate. The metal-chelating capacity and phytochemical composition of ASFE were determined. The LD50 of ASFE was evaluated by probit analysis. Molecular docking simulations were performed using Auto Dock Vina. Forty male Sprague Dawley rats were equally divided into the following groups: Gp1, a negative control group; Gp2, given ASFE (350 mg/kg body weight (b. wt.)) (1/10 of LD50); Gp3, given lead acetate (PbAc) solution (100 mg/kg b. wt.); and Gp4, given PbAc as in Gp3 and ASFE as in Gp2. All treatments were given by oro-gastric intubation daily for 30 days. Body weight changes, spermatological parameters, reproductive hormone levels, oxidative stress parameters, and inflammatory biomarkers were evaluated, and molecular and histopathological investigations were performed. The results showed that ASFE had promising metal-chelating activity and phytochemical composition. The LD50 of ASFE was 3500 mg/kg b. wt. The docking analysis showed that quercetin demonstrated a high binding affinity for JAK-1 and STAT-3 proteins, and this could make it a more promising candidate for targeting the JAK-1/STAT-3 pathway than others. The rats given lead acetate had defective testicular tissues, with altered molecular, biochemical, and histological features, as well as impaired spermatological characteristics. Treatment with ASFE led to a significant mitigation of these dysfunctions and modulated the JAK-1/STAT-3/SOCS-1 axis in the rats.

First record of Apanteles hemara (N.) on Leucinodes orbonalis Guenée and biodiversity of Hymenoptera parasitoids on Brinjal.

The brinjal fruit and shoot borer (BFSB), Leucinodes orbonalis Guenée (Lepidoptera: Crambidae), is a very detrimental pest that causes significant economic losses to brinjal crop worldwide. Infested brinjal fruits were collected from vegetable fields located at the ICAR-Indian Agricultural Research Institute (ICAR-IARI), New Delhi, India, during two consecutive seasons (2021-2022). The larvae of the pest were brought to the laboratory and reared under controlled conditions of 25 ± 0.5 °C and 70 ± 5% relative humidity, for the emergence of parasitoids. In addition, the survey of Hymenoptera parasitoids in brinjal was conducted utilizing a sweep net and yellow pan trap over the course of two seasons. The results reveal that five parasitoid species were emerged from L. orbonalis viz., Apanteles hemara Nixon, 1965, Bracon greeni Ashmead 1896 (Hymenoptera: Braconidae), Goryphus nursei (Cameron, 1907), Trathala flavoorbitalis (Cameron, 1907) (Hymenoptera: Ichneumonidae) and Spalangia gemina Boucek 1963 (Hymenoptera: Spalangiidae). Out of these, A. hemara and S. gemina were documented as new occurrences in Delhi. Additionally, A. hemara was recorded for the first time as a parasite on L. orbonalis. Trathala flavoorbitalis was observed during both seasons and exhibited higher parasitism reaching 15.55% and 18.46% in July and August 2022, respectively. However, the average parasitism (%) recorded by A. hemara, B. greeni, G. nursei, T. flavoorbitalis and S. gemina was 3.10%, 1.76%, 1.10%, 9.28% and 1.20% respectively. Furthermore, the findings showed a significant (p ≤ 0.01) strongly positive correlation between fruit infestation (%) by L. orbonalis and parasitism (%). The survey indicates the presence of a broad group (19 families and 60 species) of Hymenoptera parasitoids in the brinjal crop ecosystem in Delhi which could be valuable in biological control. In light of these results, this study revealed that A. hemara and other parasitoids identified in this study alongside T. flavoorbitalis would be ideal biocontrol agents within the integrated pest management (IPM) program of BFSB in Delhi.

Urtica pilulifera leaves extract mitigates cadmium induced hepatotoxicity via modulation of antioxidants, inflammatory markers and Nrf-2 signaling in mice.

Introduction: Cadmium (Cd) is a harmful heavy metal that results in many toxic issues. Urtica pilulifera showed potential pharmaceutical applications. This study investigated the possible ameliorative mechanism of Urtica pilulifera leaves extract (UPLE) against hepatotoxicity induced by cadmium chloride (CdCl2) in mice. Methods: In vitro phytochemical screening and the metal-chelating activity of UPLE were ascertained. Four groups of forty male mice were used (n = 10) as follows; Group 1 (G1) was a negative control. G2 was injected i.p., with UPLE (100 mg/kg b. wt) daily. G3 was injected i.p., with Cd (5 mg/kg b. wt) daily. G4 was injected with Cd as in G3 and with UPLE as in G2. On day 11, the body weight changes were evaluated, blood, and serum samples were collected for hematological and biochemical assessments. Liver tissues were used for biochemical, molecular, and histopathological investigations. Results: The results showed that UPLE contains promising secondary metabolites that considerably lessen the negative effects of Cd on liver. Furthermore, UPLE inhibited oxidative stress and inflammation; restored antioxidant molecules; and promoted nuclear-related factor-2 (Nrf-2) expression. Also, UPLE improved the histopathological alterations induced by Cd. Discussion: This study explored the beneficial role of UPLE treatment in Cd-induced liver injury through enhancing Nrf-2 signaling and antioxidant enzyme gene expression in the liver of mice. Therefore, UPLE could have valuable implications against hepatotoxicity induced by environmental cadmium exposure. Which can be used as a chelating agent against Cd.

Annona Muricata L. extract restores renal function, oxidative stress, immunohistochemical structure, and gene expression of TNF-α, IL-ß1, and CYP2E1 in the kidney of DMBA-intoxicated rats.

Introduction: 7,12-dimethylbenz (a) anthracene (DMBA) is a harmful polycyclic aromatic hydrocarbon derivative known for its cytotoxic, carcinogenic, and mutagenic effects in mammals and other species. Annona muricata, L. (Graviola; GRV) is a tropical fruit tree traditionally well-documented for its various medicinal benefits. This investigation is the first report on the potential antioxidant and antinfammatory reno-protective impact of GRV against DMBA-induced nephrotoxicity in rats. Methods: Forty male albino rats were allocated into four equal groups (n = 10). The 1st group served as the control, the 2nd group (GRV) was gastro-gavaged with GRV (200 mg/kg b.wt), the 3rd group (DMBA) was treated with a single dose of DMBA (15 mg/kg body weight), and the 4th group (DMBA + GRV) was gastro-gavaged with a single dose of DMBA, followed by GRV (200 mg/kg b.wt). The GRV administration was continued for 8 weeks. Results and Discussion: Results revealed a significant improvement in renal function, represented by a decrease in urea, creatinine, and uric acid (UA) in the DMBA + GRV group. The antioxidant potential of GRV was confirmed in the DMBA + GRV group by a significant decline in malondialdehyde (MDA) and a significant increase in catalase (CAT), superoxide dismutase (SOD), glutathione S transferase (GST), and reduced glutathione (GSH) compared to DMBA-intoxicated rats; however, it was not identical to the control. Additionally, the antiinflammatory role of GRV was suggested by a significant decline in mRNA expression of cytochrome P450, family 2, subfamily e, polypeptide 1 (CYP2E1), tumor necrosis factor-alpha (TNF-α), and interleukin 1 beta (IL-1ß) in the DMBA + GRV group. Moreover, GRV improved the histopathologic and immunohistochemical expression of TNF-α, CYP450, and IL1ß in DMBA-intoxicated kidney tissue. Conclusively, GRV is a natural medicinal product that can alleviate the renal injury resulting from environmental exposure to DMBA. The reno-protective effects of GRV may involve its anti-inflammatory and/or antioxidant properties, which are based on the presence of phytochemical compounds such as acetogenins, alkaloids, and flavonoids.

Natural sapogenins as potential inhibitors of aquaporins for targeted cancer therapy: computational insights into binding and inhibition mechanism.

Aquaporins (AQPs) are membrane proteins that facilitate the transport of water and other small molecules across biological membranes. AQPs are involved in various physiological processes and pathological conditions, including cancer, making them as potential targets for anticancer therapy. However, the development of selective and effective inhibitors of AQPs remains a challenge. In this study, we explored the possibility of using natural sapogenins, a class of plant-derived aglycones of saponins with diverse biological activities, as potential inhibitors of AQPs. We performed molecular docking, dynamics simulation and binding energy calculation to investigate the binding and inhibition mechanism of 19 sapogenins against 13 AQPs (AQP0-AQP13) that are overexpressed in various cancers. Our results showed that out of 19 sapogenins, 8 (Diosgenin, Gitogenin, Tigogenin, Ruscogenin, Yamogenin, Hecogenin, Sarsasapogenin and Smilagenin) exhibited acceptable drug-like characteristics. These sapogenin also exhibited favourable binding affinities in the range of -7.6 to -13.4 kcal/mol, and interactions within the AQP binding sites. Furthermore, MD simulations provided insights into stability and dynamics of the sapogenin-AQP complexes. Most of the fluctuations in binding pocket were observed for AQP0-Gitogenin and AQP4-Diosgenin. However, remaining protein-ligand complex showed stable root mean square deviation (RMSD) plots, strong hydrogen bonding interactions, stable solvent-accessible surface area (SASA) values and minimum distance to the receptor. These observations suggest that natural sapogenin hold promise as novel inhibitors of AQPs, offering a basis for the development of innovative therapeutic agents for cancer treatment. However, further validation of the identified compounds through experiments is essential for translating these findings into therapeutic applications.Communicated by Ramaswamy H. Sarma.

Synergistic Power of Piceatannol and/or Vitamin D in Bleomycin-Induced Pulmonary Fibrosis In Vivo: A Preliminary Study.

Oxidative stress and epigenetic alterations, including the overexpression of all class I and II histone deacetylases (HDACs), particularly HDAC2 and HDAC4, have been identified as key molecular mechanisms driving pulmonary fibrosis. Treatment with piceatannol (PIC) or vitamin D (Vit D) has previously exhibited mitigating impacts in pulmonary fibrosis models. The present study investigated the effects of PIC, Vit D, or a combination (PIC-Vit D) on the expression of HDAC2, HDAC4, and transforming growth factor-beta (TGF-ß) in the lungs; the phosphatidylinositide-3-kinase (PI3K)/AKT signaling pathway; and the antioxidant status of the lungs. The objective was to determine if the treatments had protective mechanisms against pulmonary fibrosis caused by bleomycin (BLM) in rats. Adult male albino rats were given a single intratracheal dosage of BLM (10 mg/kg) to induce pulmonary fibrosis. PIC (15 mg/kg/day, oral (p.o.)), Vit D (0.5 µg/kg/day, intraperitoneal (i.p.)), or PIC-Vit D (15 mg/kg/day, p.o. plus 0.5 µg/kg/day, i.p.) were given the day following BLM instillation and maintained for 14 days. The results showed that PIC, Vit D, and PIC-Vit D significantly improved the histopathological sections; downregulated the expression of HDAC2, HDAC4, and TGF-ß in the lungs; inhibited the PI3K/AKT signaling pathway; decreased extracellular matrix (ECM) deposition including collagen type I and alpha smooth muscle actin (α-SMA); and increased the antioxidant capacity of the lungs by increasing the levels of glutathione (GSH) that had been reduced and decreasing the levels of malondialdehyde (MDA) compared with the BLM group at a p-value less than 0.05. The concomitant administration of PIC and Vit D had a synergistic impact that was greater than the impact of monotherapy with either PIC or Vit D. PIC, Vit D, and PIC-Vit D exhibited a notable protective effect through their antioxidant effects, modulation of the expression of HDAC2, HDAC4, and TGF-ß in the lungs, and suppression of the PI3K/AKT signaling pathway.

GC-MS Analysis, Antibacterial, and Anticancer Activities of Hibiscus sabdariffa L. Methanolic Extract: In Vitro and In Silico Studies.

The emergence of bacteria that are resistant to several antibiotics has represented a serious hazard to human health globally. Bioactive metabolites from medicinal plants have a wide spectrum of therapeutic possibilities against resistant bacteria. Therefore, this study was performed to investigate the antibacterial efficacy of various extracts of three medicinal plants as Salvia officinalis L., Ziziphus spina-christi L., and Hibiscus sabdariffa L. against pathogenic Gram-negative Enterobacter cloacae (ATCC13047), Pseudomonas aeruginosa (RCMB008001), Escherichia coli (RCMB004001), and Gram-positive Staphylococcus aureus (ATCC 25923), bacteria using the agar-well diffusion method. Results revealed that, out of the three examined plant extracts, the methanol extract of H. sabdariffa L. was the most effective against all tested bacteria. The highest growth inhibition (39.6 ± 0.20 mm) was recorded against E. coli. Additionally, the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of the methanol extract of H. sabdariffa were detected in the case of all tested bacteria. Moreover, an antibiotic susceptibility test revealed that all tested bacteria showed multidrug resistance (MDR). While 50% of tested bacteria were sensitive and 50% were intermediately sensitive to piperacillin/tazobactam (TZP) based on the inhibition zone but still less than the extract. Synergistic assay demonstrated the promising role of using a combination of H. sabdariffa L. and (TZP) against tested bacteria. A surface investigation using a scanning electron microscope of the E. coli treated with TZP, extract, or a combination of the two revealed extremely considerable bacterial cell death. In addition, H. sabdariffa L. has a promising anticancer role versus Caco-2 cells with IC50 of 17.51 ± 0.07 µg/mL and minimal cytotoxicity upon testing versus Vero cells with CC50 of 165.24 ± 0.89 µg/mL. Flow cytometric analysis confirmed that H. sabdariffa extract significantly increased the apoptotic rate of Caco-2-treated cells compared to the untreated group. Furthermore, GC-MS analysis confirmed the existence of various bioactive components in the methanol hibiscus extract. Utilizing molecular docking with the MOE-Dock tool, binding interactions between n-Hexadecanoic acid, hexadecanoic acid-methyl ester, and oleic acid, 3-hydroxypropyl ester were evaluated against the target crystal structures of E. coli (MenB) (PDB ID:3T88) and the structure of cyclophilin of a colon cancer cell line (PDB ID: 2HQ6). The observed results provide insight into how molecular modeling methods might inhibit the tested substances, which may have applications in the treatment of E. coli and colon cancer. Thus, H. sabdariffa methanol extract is a promising candidate to be further investigated for developing alternative natural therapies for infection treatment.

Genetic characterization of the highlander Tibetan population from Qinghai-Tibet Plateau revealed by X chromosomal STRs.

Tibetans are considered an East Asian ethnic group and primarily live in the high Tibetan plateau, the western Sichuan and Yunnan mountains of central and southern China, and areas throughout the Himalayas and around the Tibetan plateau. These people exhibit rare molecular machinery that allows them to adapt to hypoxic environments in the Qinghai-Tibet Plateau and make them a potential candidate for providing insights related to medical genetic, molecular medicine and human population studies. In the current study, we have genotyped 549 individuals with Investigator Argus X-12 Kit. For 12 X-STRs, a total of 174 unique alleles were found, among them DXS10134 and DXS10135 were the most polymorphic loci. All of the loci were in Hardy-Weinberg Equilibrium (HWE). The numbers of observed haplotypes in Highlander Tibetans males were 161,112, 96 and 108, respectively, whereas haplotype diversities (HD) were 0.9959, 0.9880, 0.9809 and 0.9873, respectively. The combined discrimination power for males (PDm) was 0.999 999 99701 and for females (PDf) was 0.999 999 999 999 9958. This study represents an extensive report on X chromosomal STR markers variation in the Highlander Tibetans population for forensic applications and population genetic studies.