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Changes in fluid composition and expression of ion channels in rat cervix during different phases of the estrus cycle

Salleh N, Ismail N, Nelli G, Myint K, Khaing SL

Biotech Histochem, 2022 Jan;97(1):53-66.
PMID: 33827344 DOI: 10.1080/10520295.2021.1899285

We investigated changes in the composition of cervical fluid at different phases of the female rat reproductive cycle. Fluid was collected from the cervix of rats by direct cervical flushing and analyzed for changes in Na+ and Cl- content and osmolarity. Following sacrifice, the cervix was harvested and expressions of mRNA and protein for ENaCs, CFTR and AQPs were measured using qPCR and immunohistochemistry, respectively. Cervical fluid Na+ and Cl- content was high during estrus, but osmolarity was high during metestrus and diestrus. Expressions of CFTR, AQP-1 and AQP-2 in the cervix were high during estrus, but low during diestrus. Expression of ENaC (α, β, γ), AQP-5 and AQP-7 was high during metestrus and diestrus and low during estrus. Changes in expression of ion channels in the cervix could explain changes in cervical fluid composition during the estrus cycle phases that could affect female fertility.
Oral administration of Turnera diffusa willd. ex Schult. extract ameliorates steroidogenesis and spermatogenesis impairment in the testes of rats with type-2 diabetes mellitus

Kumar GG, Kilari EK, Nelli G, Bin Salleh N

J Ethnopharmacol, 2023 Oct 05;314:116638.
PMID: 37187362 DOI: 10.1016/j.jep.2023.116638

ETHNOPHARMACOLOGICAL RELEVANCE: Turnera diffusa Willd. ex Schult. (T. diffusa) has traditionally been used to treat male reproductive dysfunction and have aphrodisiac properties.
AIMS OF THE STUDY: This study aims to investigate the ability of T. diffusa to ameliorate the impairment in testicular steroidogenesis and spermatogenesis in DM that might help to improve testicular function, and subsequently restore male fertility.
MATERIALS AND METHODS: DM-induced adult male rats were given 100 mg/kg/day and 200 mg/kg/day T. diffusa leaf extract orally for 28 consecutive days. Rats were then sacrificed; sperm and testes were harvested and sperm parameter analysis were performed. Histo-morphological changes in the testes were observed. Biochemical assays were performed to measure testosterone and testicular oxidative stress levels. Immunohistochemistry and double immunofluorescence were used to monitor oxidative stress and inflammation levels in testes as well as Sertoli and steroidogenic marker proteins' expression.
RESULTS: Treatment with T. diffusa restores sperm count, motility, and viability near normal and reduces sperm morphological abnormalities and sperm DNA fragmentation in diabetic rats. T. diffusa treatment also reduces testicular NOX-2 and lipid peroxidation levels, increases testicular antioxidant enzymes (SOD, CAT, and GPx) activities, ameliorates testicular inflammation via downregulating NF-ΚB, p-Ikkβ and TNF-α and upregulating IκBα expression. In diabetic rats, T. diffusa treatment increases testicular steroidogenic proteins (StAR, CYP11A1, SHBG, and ARA54, 3 and 17β-HSD) and plasma testosterone levels. Furthermore, in diabetic rats treated with T. diffusa, Sertoli cell marker proteins including Connexin 43, N-cadherin, and occludin levels in the testes were elevated.
CONCLUSION: T. diffusa treatment could help to ameliorate the detrimental effects of DM on the testes, thus this plant has potential to be used to restore male fertility.
Gallocatechin‑silver nanoparticle impregnated cotton gauze patches enhance wound healing in diabetic rats by suppressing oxidative stress and inflammation via modulating the Nrf2/HO-1 and TLR4/NF-κB pathways

Vendidandala NR, Yin TP, Nelli G, Pasupuleti VR, Nyamathulla S, Mokhtar SI

Life Sci, 2021 Dec 01;286:120019.
PMID: 34624322 DOI: 10.1016/j.lfs.2021.120019

This study is designed to investigate the combination of gallocatechin (GC) and silver nanoparticles (AgNPs) for its wound healing ability in diabetic rats. Thirty male Sprague Dawley rats were randomly divided into 5 groups: 1. Normal control rats dressed with blank CGP1; 2. Diabetic rats dressed with blank CGP1; 3. Diabetic rats dressed with 13.06μM of GC; 4. Diabetic rats dressed with 26.12 μM of GC; 5. Diabetic rats dressed with 0.1% silver sulfadiazine patches. GC-AgNPs-CGP dressed diabetic rats showed significant FBG reduction, prevented the body weight losses and reduced the oxidative stress by lowering MDA content and elevated antioxidant enzymes such as SOD, CAT and GPx in wound healing skin of diabetic rats when compared to normal CGP. Besides, mRNA expression of Nrf2, Nqo-1, and Ho-1 was upregulated with downregulated expression of Keap-1 mRNA, which is supported by immunohistochemistry. Furthermore, GC-AgNPs-CGP dressing increased growth factors such as VEGF, EGF, TGF-β, and FGF-2 while decreasing MMP-2 in the skin of diabetic wound rats. In vitro permeation study demonstrated rapid GC release and permeation with a flux of 0.061 and 0.143 mg/sq.cm/h. In conclusion, the results indicated that GC-AgNPs-CGP dressing on diabetic wound rats modulated oxidative stress and inflammation with elevated growth factors; increased collagen synthesis thereby significantly improved the wound healing and could be beneficial for the management of diabetic wounds.
Fulltext Bitter Gourd Honey Ameliorates Hepatic and Renal Diabetic Complications on Type 2 Diabetes Rat Models by Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Mechanisms

Arigela CS, Nelli G, Gan SH, Sirajudeen KNS, Krishnan K, Abdul Rahman N, et al.

Foods, 2021 Nov 20;10(11).
PMID: 34829154 DOI: 10.3390/foods10112872

Honey has several pharmacological effects, including anti-diabetic activity. However, the effectiveness of bitter gourd honey (BGH) in the treatment of diabetes mellitus (DM) is unknown. The aim of this study was to determine the antioxidant, anti-inflammatory, and anti-apoptotic properties of BGH on the kidney and liver of a streptozotocin-induced diabetes rat model.
METHODS: A single dose (nicotinamide 110 mg/kg, streptozotocin (STZ) 55 mg/kg, intraperitoneal (i.p.)) was used to induce DM in male rats. For 28 days, normal or diabetic rats were administered 1 g/kg/day and 2 g/kg/day of BGH orally. After the treatment, blood, liver, and kidney samples were collected and analysed for biochemical, histological, and molecular parameters. In addition, liquid chromatography-mass spectrometry (LC-MS) was used to identify the major bioactive components in BGH.
RESULTS: The administration of BGH to diabetic rats resulted in significant reductions in alanine transaminase (ALT),aspartate aminotransferase (AST), creatinine, and urea levels. Diabetic rats treated with BGH showed lesser pathophysiological alterations in the liver and kidney as compared to non-treated control rats. BGH-treated diabetic rats exhibited reduced levels of oxidative stress (MDA levels), inflammatory (MYD88, NFKB, p-NFKB, IKKβ), and apoptotic (caspase-3) markers, as well as higher levels of antioxidant enzymes (SOD, CAT, and GPx) in the liver and kidney. BGH contains many bioactive compounds that may have antioxidative stress, anti-inflammatory, and anti-apoptotic effects.
CONCLUSION: BGH protected the liver and kidney in diabetic rats by reducing oxidative stress, inflammation, and apoptosis-induced damage. As a result, BGH can be used as a potential therapy to ameliorate diabetic complications.
Fulltext Exposure to High-Fat Style Diet Induced Renal and Liver Structural Changes, Lipid Accumulation and Inflammation in Intact and Ovariectomized Female Rats

Sucedaram Y, Johns EJ, Husain R, Abdul Sattar M, H Abdulla M, Nelli G, et al.

J Inflamm Res, 2021;14:689-710.
PMID: 33716510 DOI: 10.2147/JIR.S299083

Purpose: We hypothesized that low estrogen levels aggravate obesity-related complications. Diet-induced obesity can cause distinct pathologies, including impaired glucose tolerance, inflammation, and organ injury that leads to fatty liver and chronic kidney diseases. To test this hypothesis, ovariectomized (OVX) rats were fed a high-fat style diet (HFSD), and we examined structural changes and inflammatory response in the kidney and liver.
Methods: Sprague-Dawley female rats were ovariectomized or sham-operated and divided into four groups: sham-operated rats fed a normal diet (ND); ovariectomized rats fed a normal diet (OVX-ND); sham-operated rats fed a HFSD; ovariectomized rats fed a high-fat style diet (OVX-HFSD). Mean blood pressure and fasting blood glucose were measured on weeks 0 and 10. The rats were sacrificed 10 weeks after initiation of ND or HFSD, the kidney and liver were harvested for histological, immunohistochemical and immunofluorescence studies.
Results: HFSD-fed rats presented a significantly greater adiposity index compared to their ND counterparts. Liver index, fasting blood glucose and mean blood pressure was increased in OVX-HFSD rats compared to HFSD rats at study terminal. Histological and morphometric studies showed focal interstitial mononuclear cell infiltration in the kidney of HFSD rats with mesangial expansion being greater in the OVX-HFSD rats. Both HFSD fed groups showed increased expressions of renal inflammatory markers, namely TNF-alpha, IL-6 and MCP-1, and infiltrating M1 macrophages with some influence of ovarian hormonal status. HFSD-feeding also caused hepatocellular steatosis which was aggravated in ovariectomized rats fed the same diet. Furthermore, hepatocellular ballooning was observed only in the OVX-HFSD rats. Similarly, HFSD-fed rats showed increased expressions of the inflammatory markers and M1 macrophage infiltration in the liver; however, only IL-6 expression was magnified in the OVX-HFSD.
Conclusion: Our data suggest that some of the structural changes and inflammatory response in the kidney and liver of rats fed a HFSD are exacerbated by ovariectomy.