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LPS-induced Apoptosis is Partially Mediated by Hydrogen Sulphide in RAW 264.7 Murine Macrophages

George L, Ramasamy T, Sirajudeen K, Manickam V

Immunol Invest, 2019 Jul;48(5):451-465.
PMID: 30689461 DOI: 10.1080/08820139.2019.1566355

Lipopolysaccharide (LPS) induces apoptosis in murine macrophages through the autocrine secretion of tumor necrosis factor (TNF)-α and nitric oxide (NO). LPS-induced inflammation in murine macrophages is associated with hydrogen sulfide (H2S) production. In this present study, we reported the novel role of H2S in LPS-induced apoptosis and its underlying molecular mechanism specifically at late phases in murine macrophage cells. Stimulation of RAW 264.7 macrophages with LPS resulted in a time- and dose-dependent induction of apoptosis. We observed that the LPS-induced early apoptosis (associated with TNF-α secretion) in macrophages was not inhibited in the presence of H2S inhibitor (DL-propargylglycine), whereas early apoptosis was absent in the presence of TNF receptor antibody. Interestingly, LPS-induced late apoptosis paralleled with H2S production was reduced in the presence of H2S inhibitor but not with TNF receptor antibody. The late apoptotic events mediated by H2S and not the TNF-α induced early apoptosis correlated significantly with the induction of p53 and Bax expression in LPS-induced macrophages. Thus, it is possible that RAW 264.7 murine macrophages treated with LPS mediated early apoptosis through TNF-α and the late apoptotic events through the production of H2S.
Fulltext Natural Products and Their Bioactive Compounds: Neuroprotective Potentials against Neurodegenerative Diseases

Mohd Sairazi NS, Sirajudeen KNS

Evid Based Complement Alternat Med, 2020;2020:6565396.
PMID: 32148547 DOI: 10.1155/2020/6565396

In recent years, natural products, which originate from plants, animals, and fungi, together with their bioactive compounds have been intensively explored and studied for their therapeutic potentials for various diseases such as cardiovascular, diabetes, hypertension, reproductive, cancer, and neurodegenerative diseases. Neurodegenerative diseases, including Alzheimer's disease, Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis are characterized by the progressive dysfunction and loss of neuronal structure and function that resulted in the neuronal cell death. Since the multifactorial pathological mechanisms are associated with neurodegeneration, targeting multiple mechanisms of actions and neuroprotection approach, which involves preventing cell death and restoring the function to damaged neurons, could be promising strategies for the prevention and therapeutic of neurodegenerative diseases. Natural products have emerged as potential neuroprotective agents for the treatment of neurodegenerative diseases. This review focused on the therapeutic potential of natural products and their bioactive compounds to exert a neuroprotective effect on the pathologies of neurodegenerative diseases.
Studies on the antioxidant properties of Tualang honey of Malaysia

Mohamed M, Sirajudeen K, Swamy M, Yaacob NS, Sulaiman SA

Afr J Tradit Complement Altern Med, 2009 Oct 15;7(1):59-63.
PMID: 21304614

Honey has been used since ancient times for its nutritional as well as curative properties. Tualang honey is collected from wild honey bees' hives on Tualang trees found in the Malaysian rain forest. It has been used traditionally for the treatment of various diseases, where its therapeutic value has partly been related to its antioxidant properties. This study therefore assessed the colour intensity, total phenolic content, antioxidant activity and antiradical activity of gamma irradiated Tualang Honey. The colour intensity at ABS₄₅₀ was 489.5 ± 1.7 mAU, total phenolic content was 251.7 ± 7.9 mg (gallic acid) /Kg honey, total antioxidant activity by FRAP assay was 322.1 ± 9.7 (µM Fe(II)) and the antiradical activity by DPPH assay was 41.30 ± 0.78 (% inhibition). The data confirms that the antioxidant properties of gamma irradiated Tualang honey are similar to other types of honeys reported in the literature.
Fulltext Anti-inflammatory and antioxidant effects of Tualang honey in alkali injury on the eyes of rabbits: experimental animal study

Bashkaran K, Zunaina E, Bakiah S, Sulaiman SA, Sirajudeen K, Naik V

BMC Complement Altern Med, 2011;11:90.
PMID: 21982267 DOI: 10.1186/1472-6882-11-90

Alkali injury is one of the most devastating injuries to the eye. It results in permanent unilateral or bilateral visual impairment. Chemical eye injury is accompanied by an increase in the oxidative stress. Anti-inflammatory and antioxidant agents play a major role in the treatment of chemical eye injuries. The purpose of this study is to evaluate the anti-inflammatory (clinical and histopathological) and antioxidant effects of Tualang honey versus conventional treatment in alkali injury on the eyes of rabbits.
The influence of selenium status on body composition, oxidative DNA damage and total antioxidant capacity in newly diagnosed type 2 diabetes mellitus: A case-control study

Othman FB, Mohamed HJBJ, Sirajudeen KNS, Noh MFBM, Rajab NF

J Trace Elem Med Biol, 2017 Sep;43:106-112.
PMID: 28065595 DOI: 10.1016/j.jtemb.2016.12.009

Selenium is involved in the complex system of defense against oxidative stress in diabetes through its biological function of selenoproteins and the antioxidant enzyme. A case-control study was carried out to determine the association of plasma selenium with oxidative stress and body composition status presented in Type 2 Diabetes Mellitus (T2DM) patient and healthy control. This study involved 82 newly diagnosed T2DM patients and 82 healthy controls. Plasma selenium status was determined with Graphite Furnace Atomic Absorption Spectrometry. Body Mass Index, total body fat and visceral fat was assessed for body composition using Body Composition Analyzer (TANITA). Oxidative DNA damage and total antioxidant capacity were determined for oxidative stress biomarker status. In age, gender and BMI adjustment, no significant difference of plasma selenium level between T2DM and healthy controls was observed. There was as a significant difference of Oxidative DNA damage and total antioxidant capacity between T2DM patients and healthy controls with tail DNA% 20.62 [95% CI: 19.71,21.49] (T2DM), 17.67 [95% CI: 16.87,18.56] (control); log tail moment 0.41[95% CI: 0.30,0.52] (T2DM), 0.41[95% CI: 0.30,0.52] (control); total antioxidant capacity 0.56 [95% CI: 0.54,0.58] (T2DM), 0.60 [95% CI: 0.57,0.62] (control). Waist circumference, BMI, visceral fat, body fat and oxidative DNA damage in the T2DM group were significantly lower in the first plasma selenium tertile (38.65-80.90μg/L) compared to the second (80.91-98.20μg/L) and the third selenium tertiles (98.21-158.20μg/L). A similar trend, but not statistically significant, was observed in the control group.
Novel Phytochemical Constituents and Anticancer Activities of the Genus, Typhonium

Khalivulla SI, Mohammed A, Sirajudeen KNS, Shaik MI, Ye W, Korivi M

Curr Drug Metab, 2019;20(12):946-957.
PMID: 31744445 DOI: 10.2174/1389200220666191118102616

BACKGROUND: Typhonium is the largest genus in the Araceae family (~70 species), distributed in South Asia, Southeast Asia and Australia. Typhonium is well-known for its ethnopharmacological uses, and Southeast Asians consider it as an alternative medicine to treat cancer. This review elucidated the confirmed chemical structures of the isolated compounds of Typhonium and emphasized on their anticancer activities against various human cancer cells.
METHODS: Among several species, Typhonium blumei, T. flagelliforme, T. divaricatum and T. giganteum were extensively studied due to the presence of a class of secondary metabolites. All the available reports on Typhonium were included and discussed in this article.
RESULTS: Until now several groups of compounds, namely amino acids (1, 2), cinnamic acid (3), fatty acids (4-14), glycerol derivatives (15-18) and cerebrosides (19-34), flavonoids (35), hydantoins (36-38), lignin monomers (39-44), nucleobases (45-48), pheophorbides (49-52), phthalate (53), terpene and steroids (54-59) and vitamins (60, 61) were isolated and characterized from Typhonium. These phytochemicals were investigated for their anticancer properties, and results confirmed the promising growth inhibitory effect and anticancer activities against human lung, breast, prostate and colon cancer cells. The anticancer activity of these compounds appears to be mediated through the induction of apoptotic cell death. These phytochemicals further reported to exhibit other pharmacological efficacies, including anti-inflammatory, antioxidant, antiviral, anti-allergic, neuroprotective and hepato-protective properties.
CONCLUSION: This is the first review to summarize the anticancer properties of all isolated compounds of Typhonium genus with confirmed chemical structures. Further advanced studies are necessary to establish the detailed signaling pathways that are involved in the anticancer property of the compounds.
Effect of Antihypertensive Drug Treatment on Oxidative Stress Markers in Heart of Spontaneously Hypertensive Rat Models

Yusoff NSN, Mustapha Z, Sharif SET, Govindasamy C, Sirajudeen KNS

J Environ Pathol Toxicol Oncol, 2017;36(1):43-53.
PMID: 28605330 DOI: 10.1615/JEnvironPatholToxicolOncol.2017014521

Oxidative stress has been suggested to play a role in hypertension- and hypertension-induced organ damage. The effect of antihypertensive drug treatments on oxidative stress markers has not been well assessed. Therefore, in this study we investigated the effect of enalapril on oxidative stress markers in hearts of hypertensive rat models such as spontaneously hypertensive rats (SHR) and SHRs administered N-nitro-L-arginine methyl ester (SHR+L-NAME rats). Male rats were divided into four groups: SHRs, SHR+enalapril (SHR-E) rats, SHR+L-NAME rats, SHR+enalapril+L-NAME (SHRE+L-NAME) rats. Rats (SHREs) were administered enalapril (30 mg kg-1 day-1) in drinking water from week 4 to week 28 and L-NAME (25 mg kg-1 day-1) from week 16 to week 28 in drinking water. At the end of 28 weeks, animals were sacrificed, and their hearts were collected for the assessment of oxidative stress markers and histological examination. Enalapril treatment significantly enhanced the total antioxidant status (TAS) (P < 0.001), reduced the oxidized glutathione ratio (GSH : GSSG) (P < 0.001), and reduced to thibarbituric acid reactive substances (TBARS) (P < 0.001) and protein carbonyl content (PCO) (P < 0.001), which thus reduced the oxidative stress in the heart. The fibrosis areas in SHRs and SHR+L-NAME rats were also markedly reduced. These findings suggest that enalapril might play a protective role in hypertension- and hypertension-induced organ damage.
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 Tualang Honey Reduced Neuroinflammation and Caspase-3 Activity in Rat Brain after Kainic Acid-Induced Status Epilepticus

Mohd Sairazi NS, Sirajudeen KNS, Muzaimi M, Mummedy S, Asari MA, Sulaiman SA

Evid Based Complement Alternat Med, 2018;2018:7287820.
PMID: 30108663 DOI: 10.1155/2018/7287820

The protective effect of tualang honey (TH) on neuroinflammation and caspase-3 activity in rat cerebral cortex, cerebellum, and brainstem after kainic acid- (KA-) induced status epilepticus was investigated. Male Sprague-Dawley rats were pretreated orally with TH (1.0 g/kg body weight) five times at 12 h intervals. KA (15 mg/kg body weight) was injected subcutaneously 30 min after last oral treatment. Rats were sacrificed at 2 h, 24 h, and 48 h after KA administration. Neuroinflammation markers and caspase-3 activity were analyzed in different brain regions 2 h, 24 h, and 48 h after KA administration. Administration of KA induced epileptic seizures. KA caused significant (p < 0.05) increase in the level of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), glial fibrillary acidic protein (GFAP), allograft inflammatory factor 1 (AIF-1), and cyclooxygenase-2 (COX-2) and increase in the caspase-3 activity in the rat cerebral cortex, cerebellum, and brainstem at multiple time points. Pretreatment with TH significantly (p < 0.05) reduced the elevation of TNF-α, IL-1β, GFAP, AIF-1, and COX-2 level in those brain regions at multiple time points and attenuated the increased caspase-3 activity in the cerebral cortex. In conclusion, TH reduced neuroinflammation and caspase-3 activity after kainic acid- (KA-) induced status epilepticus.
Fulltext Sulfated glycosaminoglycans from crown-of-thorns Acanthaster planci - extraction and quantification analysis

Bahrom NA, Sirajudeen K, Yip GW, Latiff AA, Ghazali FC

Food Sci Nutr, 2013 Jan;1(1):83-9.
PMID: 24804017 DOI: 10.1002/fsn3.10

In this article, the novel inventive steps for the extraction and quantification of sulfated glycosaminoglycan (GAG) from Acanthaster planci starfish, generally known as crown-of-thorns (COT), are reported. Starfish have been implicated with collagenous distributions within their body anatomy, thus making it a prima facie fact searching for the possibility that GAGs can be isolated from COT. In this study, total-, N-, and O-sulfated GAGs were extracted from three anatomical regions of the COT (integument, internal tissue, and coelomic fluid) and comparison was made. The result showed that body region of COT seemed to contain higher amount of sulfated GAGs as opposed to the arm region (55.79 ± 0.65 μg/mg was the highest amount in the body extracted from its coelomic fluid and 32.28 ± 3.14 μg/mg was the highest amount in the arm extracted from its internal tissue). COT's integument and coelomic fluid from its body region possessed the highest total of sulfated GAGs content with no significant difference (P
Fulltext Tualang honey and DHA-rich fish oil reduce the production of pro-inflammatory cytokines in the rat brain following exposure to chronic stress

Asari MA, Zulkaflee MH, Sirajudeen KNS, Mohd Yusof NA, Mohd Sairazi NS

J Taibah Univ Med Sci, 2019 Aug;14(4):317-323.
PMID: 31488962 DOI: 10.1016/j.jtumed.2019.06.004

OBJECTIVES: The aim of the present study was to investigate the effects of Tualang honey (TH), DHA-rich fish oil, and their combination on the concentrations of selected pro-inflammatory cytokines in rat brains following exposure to chronic stress.
METHODS: Fifty male Sprague-Dawley rats were divided into (i) control, (ii) stress-exposed, (iii) stress-exposed and treated with TH (1 g/kg body weight twice daily via oral gavage), (iv) stress-exposed and treated with DHA-rich fish oil (450 mg/kg body weight twice daily via oral gavage), and (v) stress-exposed and treated with a combination of TH and DHA-rich fish oil. The chronic stress regimen consisted of a combination of restraint stress and a swim stress test for 28 days. The concentrations of selected pro-inflammatory cytokines in brain homogenates (TNF-α, IL6, and IFN-γ) were measured by ELISA.
RESULTS: The concentrations of TNF-α, IL6, and IFN-γ in brain homogenates from the DHA, TH, and TH + DHA-treated groups were significantly lower compared to the control and stress-only-exposed groups (p
Fulltext Anthropometric and reproductive factors among newly- diagnosed breast cancer patients and healthy women: a case-control study

Zunura'in Z, Almardhiyah AR, Gan SH, Arifin WN, Sirajudeen K, Bhavaraju V, et al.

Asian Pac J Cancer Prev, 2016;17(9):4439-4444.
PMID: 27797258

The objective of this case-control study was to determine anthropometric and reproductive factors associated with the development of breast cancer among women. Fifty-six newly diagnosed breast cancer patients were recruited from the Oncology Clinic, Universiti Sains Malaysia (USM), and 56 healthy female hospital employees were recruited as controls. Socio-demographic and reproductive data were obtained using a standard questionnaire. Anthropometric factors (body weight, height, body fat percentage, visceral fat and waist and hip circumference) were assessed. A high waist circumference (adjusted OR= 1.04, [95% CI: 1.00, 1.09]) and being more than 30 years of age at rst full-term pregnancy (adjusted OR=3.77, [95% CI: 1.10, 12.90]) were predictors of breast cancer development. The results of this study indicate that weight and reproductive health management should be emphasized for breast cancer prevention in Malaysia.

Study site: Oncology clinic, Hospital Universiti Sains Malaysia (HUSM)
Fulltext Profiling the Research Landscape on Cognitive Aging: A Bibliometric Analysis and Network Visualization

Othman Z, Abdul Halim AS, Azman KF, Ahmad AH, Zakaria R, Sirajudeen KNS, et al.

Front Aging Neurosci, 2022;14:876159.
PMID: 35572132 DOI: 10.3389/fnagi.2022.876159

OBJECTIVES: This study aimed to profile the cognitive aging research landscape from 1956 to 2021.
METHODS: A total of 3,779 documents were retrieved from the Scopus database for the bibliometric analysis and network visualization. By comparing each keyword's overall connection strength (centrality), frequency (density), and average year of publication (novelty) to the calculated median values acquired from the overlay view of the VOSviewer map, the enhanced strategic diagrams (ESDs) were constructed.
RESULTS: The findings showed an increasing trend in the number of publications. The United States leads the contributing countries in cognitive aging research. The scientific productivity pattern obeyed Lotka's law. The most productive researcher was Deary, I. J., with the highest number of publications. The collaborative index showed an increasing trend from 1980 onwards. Frontiers in Aging Neuroscience is the most prestigious journal in the field of cognitive aging research. In Bradford core journals zone 1, the top 10 core journals of cognitive aging research provided more than half of the total articles (697, or 55.36 percent).
CONCLUSIONS: For the next decades, the trending topics in cognitive aging research include neuropsychological assessment, functional connectivity, human immunodeficiency virus (HIV), decision-making, gender, compensation, default mode network, learning and memory, brain-derived neurotrophic factor (BDNF), obesity, D-galactose, epigenetics, frailty, mortality, mini-mental state examination (MMSE), anxiety, and gait speed.
Fulltext Association between Vitamin D Receptor Polymorphisms (BsmI and FokI) and Glycemic Control among Patients with Type 2 Diabetes

Zakaria WNA, Mohd Yunus N, Yaacob NM, Omar J, Wan Mohamed WMI, Sirajudeen KNS, et al.

Int J Environ Res Public Health, 2021 Feb 08;18(4).
PMID: 33567588 DOI: 10.3390/ijerph18041595

(1) Background: Several studies have suggested that the vitamin D receptor (VDR) gene plays a role in type 2 diabetes mellitus (T2DM) susceptibility. Nonetheless, the association between T2DM and VDR polymorphisms remains inconclusive. We determined the genotype of VDR rs1544410 (BsmI) and rs2228570 (FokI) polymorphisms among Malaysian patients with T2DM and their association with glycemic control factors (vitamin D levels, calcium, magnesium, and phosphate). (2) Methods: A total of 189 participants comprising 126 patients with T2DM (63 with good glycemic control and 63 with poor glycemic control) and 63 healthy controls were enrolled in this case-control study. All biochemical assays were measured using spectrophotometric analysis. VDR gene FokI and BsmI polymorphisms were analyzed using polymerase chain reaction and endonuclease digestion. (3) Results: Our findings revealed no significant differences in VDR FokI and BsmI genotypes between participants with T2DM and healthy controls. Moreover, no significant association was observed between both single nucleotide polymorphisms and glycemic control factors. Participants with poor glycemic control had significantly lower serum magnesium levels and significantly higher HOMA-IR compared to the other groups. (4) Conclusions: The present study revealed that VDR gene BsmI and FokI polymorphisms were not significantly associated with T2DM.
Fulltext Evaluation of Chondroprotective Activity of Channa striatus in Rabbit Osteoarthritis Model

Abdul Kadir A, Abdul Kadir A, Abd Hamid R, Mat Jais AM, Omar J, Sadagatullah AN, et al.

Biomed Res Int, 2019;2019:6979585.
PMID: 31355276 DOI: 10.1155/2019/6979585

Objectives: The objective of the study is to evaluate the chondroprotective activity of Channa striatus (Channa) and glucosamine sulphate (glucosamine) on histomorphometric examinations, serum biomarker, and inflammatory mediators in experimental osteoarthritis (OA) rabbit model.
Design: Anterior cruciate ligament transection (ACLT) was performed to induce OA in thirty-three male New Zealand white rabbits and were randomly divided into three groups: Channa, glucosamine, and control group. The control group received drinking water and the Channa and glucosamine groups were orally administered with 51.4 mg/kg of Channa extract and 77.5 mg/kg of glucosamine sulphate in drinking water, respectively, for eight weeks and then sacrificed. The articular cartilage was evaluated macroscopically and histologically using semiquantitative and quantitative methods. Serum cartilage oligomeric matric protein (COMP), cyclooxygenase 2 (COX-2) enzyme, and prostaglandin E2 (PGE2) were also determined.
Results: Macroscopic analysis revealed that Channa group have a significantly lower severity grade of total macroscopic score compared to the control (p < 0.001) and glucosamine (p < 0.05) groups. Semiquantitative histology scoring showed that both Channa and glucosamine groups had lower severity grading of total histology score compared to the control group (p < 0.001). In comparison with the control, Channa group had lower histopathological changes in three compartments of the joint compared to glucosamine group which had lower histological scoring in two compartments only. The cartilage thickness, area, and roughness of both Channa (p < 0.05) and glucosamine (p < 0.05) groups were superior compared to the control group. However, the Channa group demonstrated significantly less cartilage roughness compared to the glucosamine group (p < 0.05). Serum COMP levels were lower in both Channa (p < 0.05) and glucosamine (p < 0.05) groups compared to the control group.
Conclusion: Both oral administration of Channa extract and glucosamine exhibited chondroprotective action on an ACLT OA-induced rabbit model. However, Channa was superior to glucosamine in maintaining the structure of the cartilage.
Fulltext Hepatic and renal effects of oral stingless bee honey in a streptozotocin-induced diabetic rat model

Mohd Nasir S, Ismail AF, Tuan Ismail TS, Wan Abdul Rahman WF, Wan Ahmad WAN, Tengku Din TADA, et al.

World J Exp Med, 2024 Mar 20;14(1):91271.
PMID: 38590306 DOI: 10.5493/wjem.v14.i1.91271

BACKGROUND: Diabetes is known damage the liver and kidney, leading to hepatic dysfunction and kidney failure. Honey is believed to help in lowering the blood glucose levels of diabetic patients and reducing diabetic complications. However, the effect of stingless bee honey (SBH) administration in relieving liver and kidney damage in diabetes has not been well-studied.
AIM: To investigate the effect of SBH administration on the kidney and liver of streptozotocin-induced (STZ; 55 mg/kg) diabetic Sprague Dawley rats.
METHODS: The rats were grouped as follows (n = 6 per group): non-diabetic (ND), untreated diabetic (UNT), metformin-treated (MET), and SBH+metformin-treated (SBME) groups. After successful diabetic induction, ND and UNT rats were given normal saline, whereas the treatment groups received SBH (2.0 g/kg and/or metformin (250 mg/kg) for 12 d. Serum biochemical parameters and histological changes using hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining were evaluated.
RESULTS: On H&E and PAS staining, the ND group showed normal architecture and cellularity of Bowman's capsule and tubules, whereas the UNT and MET groups had an increased glomerular cellularity and thickened basement membrane. The SBH-treated group showed a decrease in hydropic changes and mild cellularity of the glomerulus vs the ND group based on H&E staining, but the two were similar on PAS staining. Likewise, the SBME-treated group had an increase in cellularity of the glomerulus on H&E staining, but it was comparable to the SBH and ND groups on PAS staining. UNT diabetic rats had tubular hydropic tubules, which were smaller than other groups. Reduced fatty vacuole formation and dilated blood sinusoids in liver tissue were seen in the SBH group. Conversely, the UNT group had high glucose levels, which subsequently increased MDA levels, ultimately leading to liver damage. SBH treatment reduced this damage, as evidenced by having the lowest fasting glucose, serum alanine transaminase, aspartate transaminase, and alkaline phosphatase levels compared to other groups, although the levels of liver enzymes were not statistically significant.
CONCLUSION: The cellularity of the Bowman's capsule, as well as histological alteration of kidney tubules, glomerular membranes, and liver tissues in diabetic rats after oral SBH resembled those of ND rats. Therefore, SBH exhibited a protective hepatorenal effect in a diabetic rat model.

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