Displaying publications 1 - 20 of 66 in total

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  1. Aziz NF, Ramalingam A, Latip J, Zainalabidin S
    Life Sci, 2021 Mar 15;269:119080.
    PMID: 33465387 DOI: 10.1016/j.lfs.2021.119080
    S-Allylcysteine (SAC) is an extensively studied natural product which has been proven to confer cardioprotection. This potentiates SAC into many clinical relevance possibilities, hence, the use of it ought to be optimally elucidated. To further confirm this, an ischemia/reperfusion model has been used to determine SAC at 10 mM and 50 mM on cardiac function, cardiac marker, and mitochondrial permeability. Using Langendorff setup, 24 adult male Wistar rats' hearts were isolated to be perfused with Kreb-Henseleit buffer throughout the ischemia/reperfusion method. After 20 min of stabilization, global ischemia was induced by turning off the perfusion for 35 min followed by 60 min of reperfusion with either Kreb-Henseleit buffer or SAC with the dose of 10 mM or 50 mM. The cardiac function was assessed and coronary effluent was collected at different timepoints throughout the experiment for lactate dehydrogenase (LDH) measurement. The harvested hearts were then used to measure glutathione while isolated mitochondria for mPTP analysis. SAC-reperfused hearts were shown to prevent the aggravation of cardiac function after I/R induction. It also dose-dependently upregulated glutathione reductase and glutathione level and these were also accompanied by significant reduction of LDH leakage and preserved mitochondrial permeability. Altogether, SAC dose-dependently was able to recover the post-ischemic cardiac function deterioration alongside with improvement of glutathione metabolism and mitochondrial preservation. These findings highly suggest that SAC when sufficiently supplied to the heart would be able to prevent the deleterious complications after the ischemic insult.
  2. Si LY, Ali SAM, Latip J, Fauzi NM, Budin SB, Zainalabidin S
    Life Sci, 2017 Dec 15;191:157-165.
    PMID: 29066253 DOI: 10.1016/j.lfs.2017.10.030
    AIMS: Obesity increase the risks of hypertension and myocardial infarction (MI) mediated by oxidative stress. This study was undertaken to investigate the actions of roselle aqueous extract (R) on cardiotoxicity in obese (OB) rats and thereon OB rats subjected to MI.

    MAIN METHODS: Male Sprague-Dawley rats were fed with either normal diet or high-fat diet for 8weeks. Firstly, OB rats were divided into (1) OB and (2) OB+R (100mg/kg, p.o, 28days). Then, OB rats were subjected to MI (ISO, 85mg/kg, s.c, 2days) and divided into three groups: (1) OB+MI, (2) OB+MI+R and (3) OB+MI+enalapril for another 4weeks.

    KEY FINDINGS: Roselle ameliorated OB and OB+MI's cardiac systolic dysfunction and reduced cardiac hypertrophy and fibrosis. The increased oxidative markers and decreased antioxidant enzymes in OB and OB+MI groups were all attenuated by roselle.

    SIGNIFICANCE: These observations indicate the protective effect of roselle on cardiac dysfunction in OB and OB+MI rats, which suggest its potential to be developed as a nutraceutical product for obese and obese patients with MI in the future.

  3. Tobuse AJ, Ang CW, Yeong KY
    Life Sci, 2022 Aug 01;302:120660.
    PMID: 35642852 DOI: 10.1016/j.lfs.2022.120660
    With the continuous evolution of bacteria, the global antimicrobial resistance health threat is causing millions of deaths yearly. While depending on antibiotics as a primary treatment has its merits, there are no effective alternatives thus far in the pharmaceutical market against some drug-resistant bacteria. In recent years, vaccinology has become a key topic in scientific research. Combining with the growth of technology, vaccine research is seeing a new light where the process is made faster and more efficient. Although less discussed, bacterial vaccine is a feasible strategy to combat antimicrobial resistance. Some vaccines have shown promising results with good efficacy against numerous multidrug-resistant strains of bacteria. In this review, we aim to discuss the findings from studies utilizing reverse vaccinology for vaccine development against some multidrug-resistant bacteria, as well as provide a summary of multi-year bacterial vaccine studies in clinical trials. The advantages of reverse vaccinology in the generation of new bacterial vaccines are also highlighted. Meanwhile, the limitations and future prospects of bacterial vaccine concludes this review.
  4. Ooi BK, Phang SW, Yong PVC, Chellappan DK, Dua K, Khaw KY, et al.
    Life Sci, 2021 Aug 01;278:119658.
    PMID: 34048809 DOI: 10.1016/j.lfs.2021.119658
    AIMS: Maslinic acid (MA) is a naturally occurring pentacyclic triterpene known to exert cardioprotective effects. This study aims to investigate the involvement of nuclear factor erythroid 2-related factor 2 (Nrf2) for MA-mediated anti-inflammatory effects in atheroma pathogenesis in vitro, including evaluation of tumor necrosis factor-alpha (TNF-α)-induced monocyte recruitment, oxidized low-density lipoprotein (oxLDL)-induced scavenger receptors expression, and nuclear factor-kappa B (NF-ĸB) activity in human umbilical vein endothelial cells (HUVECS) and human acute monocytic leukemia cell line (THP-1) macrophages.

    MATERIALS AND METHODS: An in vitro monocyte recruitment model utilizing THP-1 and HUVECs was developed to evaluate TNF-α-induced monocyte adhesion and trans-endothelial migration. To study the role of Nrf2 for MA-mediated anti-inflammatory effects, Nrf2 inhibitor ML385 was used as the pharmacological inhibitor. The expression of Nrf2, monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule 1 (VCAM-1), cluster of differentiation 36 (CD36), and scavenger receptor type A (SR-A) in HUVECs and THP-1 macrophages were investigated using RT-qPCR and Western blotting. The NF-κB activity was determined using NF-κB (p65) Transcription Factor Assay Kit.

    KEY FINDINGS: The results showed opposing effects of MA on Nrf2 expression in HUVECs and THP-1 macrophages. MA suppressed TNF-α-induced Nrf2 expression in HUVECs, but enhanced its expression in THP-1 macrophages. Combined effects of MA and ML385 suppressed MCP-1, VCAM-1, and SR-A expressions. Intriguingly, at the protein level, ML385 selectively inhibited SR-A but enhanced CD36 expression. Meanwhile, ML385 further enhanced MA-mediated inhibition of NF-κB activity in HUVECs. This effect, however, was not observed in THP-1 macrophages.

    SIGNIFICANCE: MA attenuated foam cell formation by suppressing VCAM-1, MCP-1, and SR-A expression, as well as NF-κB activity, possibly through Nrf2 inhibition. The involvement of Nrf2 for MA-mediated anti-inflammatory effects however differs between HUVECs and macrophages. Future investigations are warranted for a detailed evaluation of the contributing roles of Nrf2 in foam cells formation.

  5. Loh YC, Chan SY, Tew WY, Oo CW, Yam MF
    Life Sci, 2020 May 15;249:117512.
    PMID: 32145305 DOI: 10.1016/j.lfs.2020.117512
    Hypertension is one of the leading causes of mortality in relation to the cardiovascular conditions and easily the most overlooked and poorly managed disease in mankind. With well over 200 drugs available in the market globally, there is still an urgency to search for antihypertensive alternatives due to the subpar efficacy and unwarranted side effects of the current choices. Present studies reported over 250 types of plant-derived compounds were being investigated for potential pharmacological effects on the vasculature in the last 3 decades. There were numerous literatures that claimed various compounds exhibiting vasorelaxant properties to a certain extent with low numbers of these compounds being successfully adapted into the current medicinal practice for treatment of hypertension. The issue is the scarcity of reviews that summarizes the discovery of this field and the lack of thorough comparison of these compounds to identify which of these vasodilators should be the next face of hypertension management. Thus, this review is aiming towards identifying the relationship between a major class of plant-derived compounds, flavonoid's activity as a vasodilator with their signalling pathways and their structural characteristics according to their vasorelaxant properties. Interestingly, we found that both nitric oxide and voltage-operated calcium channels pathways, and two of the flavonoid's structural characteristics play crucial roles in eliciting strong vasorelaxant effects. We have faith that the insights of this review will serve as a reference for those researching similar topics in the future and potentially lead to the development of more promising antihypertensive alternative.
  6. Loh YC, Chan SY, Oo CW, Yam MF
    Life Sci, 2021 Aug 01;278:119560.
    PMID: 33915131 DOI: 10.1016/j.lfs.2021.119560
    AIMS: The structure-vasorelaxant activity relationships (SARs) assessment in previous study has found that trans-3,4,4'-trihydroxystilbene (344OH) could potentially act as a vasorelaxing agent with demonstration of over 2-fold maximal relaxation (Rmax) compared to its analogue, resveratrol. The present study focuses on the mechanism of actions and pathways employed by 344OH and compared to its analogue to further speculate the SAR of stilbenoids towards vasorelaxation.

    MATERIALS AND METHODS: The 344OH employed in present study was synthesized based on the protocol in previous study. The vascular responses towards the cumulative addition of 344OH were evaluated using in vitro rat aortic rings assays.

    KEY FINDINGS: The pEC50 and Rmax values were found to be 4.33 ± 0.05 and 106 ± 3.99%, respectively. Results showed that the vasorelaxation of 344OH were predominated by G-protein-coupled muscarinic- (M3) and β2-adrenergic receptors, followed by PGI2/AC/cAMP- and NO/sGC/cGMP-dependent pathways. It was also identified that 344OH employed voltage-activated- (Kv), calcium-activated- (Kca) and inwardly-rectifying (Kir) potassium channels and act as an antagonist for both VOCC and IP3R while regulating the action potential in the vasculature.

    SIGNIFICANCE: The different position of hydroxyl substituent located in A-ring of the stilbenoid backbone in 344OH compared to resveratrol resulted in a significant difference in mechanistic actions that lead to 344OH's fast-acting and less time-dependent vasorelaxation behaviour. This has substantially increased the potential of 344OH to be developed as an effective antihypertensive drug in future. Present findings further strengthen our inferences where the SARs study approach should be carried out as the mainstream methodology in future drug development research.

  7. Shao Y, Dang M, Lin Y, Xue F
    Life Sci, 2019 Aug 15;231:116422.
    PMID: 31059689 DOI: 10.1016/j.lfs.2019.04.048
    This study was performed to evaluate the antidiabetic and wound healing activity of plumbagin in diabetic rats by macroscopical, biochemical, histological, immunohistochemical and molecular methods. Percentage of wound closure and contraction was delayed in diabetic rats when compared to non-diabetic group. There was significant reduction in period of epithelialization, collagen and protein content. Serum insulin level was significantly lowered together with increase in glucose level in diabetic rats. Lipid levels were increased significantly with concomitant decrease in HDL level. The mRNA levels of Nrf2, collagen-1, TGF-β and α-SMA were significantly lowered whereas Keap-1 levels were increased in diabetic rats. The level of lipid peroxides was increased while the levels of antioxidants were lowered significantly. ELISA results reveal upregulated levels of inflammatory markers. Western blot result shows upregulated levels of CD68 and CD163 proteins in wound area of diabetic rats. Histopathological observation revealed increased inflammatory cells infiltration in diabetic control. Immunofluorescent staining and immunohistochemical analysis also displayed delayed wound healing in diabetic groups. Diabetic rats treated with 10% and 20% plumbagin showed increased epithelialization, collagen deposition, increased serum insulin level and increased antioxidant status. Lipid peroxides and lipid levels were lowered significantly with increase in HDL level. Inflammatory markers were lowered, and growth factors expressions were increased markedly. Thus, the results of the study indicated that plumbagin administration could improve wound healing activity and could serve as a potent antidiabetic and anti-inflammatory agent.
  8. Khor ES, Noor SM, Wong PF
    Life Sci, 2016 Apr 1;150:67-75.
    PMID: 26916825 DOI: 10.1016/j.lfs.2016.02.076
    MicroRNAs (miRNAs) are vital in modulating lifespan and various biological processes including vascular function. The pivotal roles of mammalian target of rapamycin (mTOR) in regulating senescence and angiogenesis have been extensively described. However, the roles of its orthologue, zebrafish target of rapamycin (zTOR) in senescence and angiogenesis remain to be unravelled. In the present study, we aimed to investigate the role of zTOR and identify miRNAs associated with senescence and angiogenesis.
  9. Yahya MD, Watson RR
    Life Sci, 1987 Dec 07;41(23):2503-10.
    PMID: 2824957
    The immunomodulatory effects of morphine and the active components of marijuana, particularly tetrahydrocannabinol, on various aspects of the host immune parameters include alterations in humoral, cell-mediated and innate immunity. Most studies have shown immunosuppressive effects due to use of these abused substances, although there are reports that they may not produce any deleterious effect and may even enhance some aspects of host immunity. They reduce resistance to cancer growth and microbial pathogens in animals.
  10. Phua CYH, Teoh ZL, Goh BH, Yap WH, Tang YQ
    Life Sci, 2021 Nov 08;287:120120.
    PMID: 34762903 DOI: 10.1016/j.lfs.2021.120120
    Cancer is a heterogeneous disease with high morbidity and mortality rate involving changes in redox balance and deregulation of redox signalling. For decades, studies have involved developing an effective cancer treatment to combat treatment resistance. As natural products such as thymoquinone have numerous health benefits, studies are also focusing on using them as a viable method for cancer treatment, as they have minimal toxic effects compared with standard cancer treatments. Thymoquinone studies have shown numerous mechanisms of action, such as regulation of reactive species interfering with DNA structure, modulating various potential targets and their signalling pathways as well as immunomodulatory effects in vitro and in vivo. Thymoquinone's anti-cancer effect is mainly due to the induction of apoptotic mechanisms, such as activation of caspases, downregulation of precancerous genes, inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), anti-tumour cell proliferation, ROS regulation, hypoxia and anti-metastasis. Insight into thymoquinone's potential as an alternative treatment for chemoprevention and inflammation can be accomplished via compiling these studies, to provide a better understanding on how and why it works, as well as its interactions with common chemotherapeutic treatments.
  11. Tang KS
    Life Sci, 2019 Sep 15;233:116695.
    PMID: 31351082 DOI: 10.1016/j.lfs.2019.116695
    Alzheimer's disease (AD) is neurodegenerative disorder that is associated with memory and cognitive decline in the older adults. Scopolamine is commonly used as a behavioral model in studying cognitive disorders including AD. Many studies have also concurrently examined the neurochemical mechanisms underlying the behavioral modifications by scopolamine treatment. Nonetheless, the scopolamine model has not become a standard tool in the early assessment of drugs. Furthermore, the use of scopolamine as a pharmacological model to study AD remains debatable. This report reviews the scopolamine-induced cellular and molecular changes and discusses how these changes relate to AD pathogenesis.
  12. Tang KS
    Life Sci, 2020 Oct 15;259:118287.
    PMID: 32814066 DOI: 10.1016/j.lfs.2020.118287
    Alzheimer's disease (AD) is a fatal neurodegenerative disease that requires immediate attention. Oxidative stress that leads to the generation of reactive oxygen species is a contributing factor to the disease progression by promoting synthesis and deposition of amyloid-β, the main hallmark protein in AD. It has been previously demonstrated that nanoyttria possesses antioxidant properties and can alleviate cellular oxidative injury in various toxicity and disease models. This review proposed that nanoyttria could be used for the treatment of AD. In this paper, the evidence on the antioxidant potential of nanoyttria is presented and its prospects on AD therapy are discussed.
  13. Tang KS
    Life Sci, 2019 Dec 15;239:117011.
    PMID: 31669241 DOI: 10.1016/j.lfs.2019.117011
    Diabetes mellitus (DM) is a multifaceted and costly disease, which requires serious attention. Finding a cheaper anti-diabetic alternative that can act on multiple disease-related targets and pathways is the ultimate treatment goal for DM. Nanotechnology has offered some exciting possibilities in biomedical and drug delivery applications. Zinc oxide nanoparticles (ZnO-NPs), a novel agent to deliver zinc, have great implications in many disease therapies including DM. This review summarizes the pharmacological mechanisms by which ZnO-NPs alleviate DM and diabetic complications. Research implications and future perspectives were also discussed.
  14. Wang D, Tan KS, Zeng W, Li S, Wang Y, Xu F, et al.
    Life Sci, 2022 Mar 15;293:120336.
    PMID: 35065166 DOI: 10.1016/j.lfs.2022.120336
    AIMS: Individuals with nonalcoholic hepatosteatosis (NAFLD) have a worse atherogenic lipoprotein profile and are susceptible to cardiovascular diseases. The MEK-ERK signaling cascades are central regulators of the levels of LDL receptor (LDLR), a major determinant of circulating cholesterol. It is elusive how hepatic steatosis contributes to dyslipidemia, especially hypercholesterolemia.

    MAIN METHODS: The effects of BChE on signaling pathways were determined by immunoblotting in a BChE knockout hepatocyte cell line. DiI-LDL probe was used to explore the effect of BChE expression on LDL internalization. Co-immunoprecipitation and LC-MS were used to explore the interacting proteins with BChE. Finally, a hepatocyte-restricted BChE silencing mouse model was established by AAV8-Tbg-shRNA, and the hypercholesterolemia was induced by 65% kcal% high-fat, high-sucrose diet feeding.

    MAIN FINDINGS: Here we demonstrate that butyrylcholinesterase (BChE) governs the LDL receptor levels and LDL uptake capacity through the MEK-ERK signaling cascades to promote Ldlr transcription. BChE interacts and co-localizes with PRMT5, a protein methylation modifier controlling the ERK signaling. PRMT5 regulates LDLR-dependent LDL uptake and is a substrate of chaperone-mediated autophagy (CMA). BChE deficiency induces the PRTM5 degradation dependent on CMA activity, possibly through facilitating the HSC70 (Heat shock cognate 71 kDa) recognition of PRMT5. Remarkably, in vivo hepatocyte-restricted BChE silencing reduces plasma cholesterol levels substantially. In contrast, the BChE knockout mice are predisposed to hypercholesterolemia.

    SIGNIFICANCE: Taken together, these findings outline a regulatory role for the BChE-PRMT5-ERK-LDLR axis in hepatocyte cholesterol metabolism, and suggest that targeting liver BChE is an effective therapeutic strategy to treat hypercholesterolemia.

  15. Ooi JP, Kuroyanagi M, Sulaiman SF, Muhammad TS, Tan ML
    Life Sci, 2011 Feb 28;88(9-10):447-54.
    PMID: 21219911 DOI: 10.1016/j.lfs.2010.12.019
    Cytochrome P450 (CYP) enzymes have been implicated in a large number of preventable drug-herb interactions. Andrographis paniculata Nees, a tropical herb widely used for various health conditions contains two major diterpenoids, andrographolide and 14-Deoxy-11, 12-Didehydroandrographolide. These compounds were evaluated systematically for their effects on CYP1A2, CYP2D6 and CYP3A4 expressions in HepG2 cells.
  16. Shahcheraghi SH, Aljabali AAA, Al Zoubi MS, Mishra V, Charbe NB, Haggag YA, et al.
    Life Sci, 2021 Aug 01;278:119632.
    PMID: 34019900 DOI: 10.1016/j.lfs.2021.119632
    Diabetes epidemiological quantities are demonstrating one of the most important communities' health worries. The essential diabetic difficulties are including cardiomyopathy, nephropathy, inflammation, and retinopathy. Despite developments in glucose decreasing treatments and drugs, these diabetic complications are still ineffectively reversed or prohibited. Several signaling and molecular pathways are vital targets in the new therapies of diabetes. This review assesses the newest researches about the key molecules and signaling pathways as targets of molecular pharmacology in diabetes and diseases related to it for better treatment based on molecular sciences. The disease is not cured by current pharmacological strategies for type 2 diabetes. While several drug combinations are accessible that can efficiently modulate glycemia and mitigate long-term complications, these agents do not reverse pathogenesis, and in practice, they are not established to modify the patient's specific molecular profiling. Therapeutic companies have benefited from human genetics. Genome exploration, which is agnostic to the information that exists, has revealed tens of loci that impact glycemic modulation. The physiological report has begun to examine subtypes of diseases, illustrate heterogeneity and propose biochemical therapeutic pathways.
  17. Israf DA, Lajis NH, Somchit MN, Sulaiman MR
    Life Sci, 2004 Jun 11;75(4):397-406.
    PMID: 15147827
    An experiment was conducted with the objective to enhance mucosal immunity against ovalbumin (OVA) by co-administration of OVA with an aqueous extract from the fruit of Solanum torvum (STE). Five groups of female ICR mice aged approximately 8 weeks at the commencement of the experiment were caged in groups of eight and received various treatments. The treatments included OVA alone, OVA with cholera toxin (CT), and OVA with various doses of STE. Mice were primed intraperitoneally with 500 microg of OVA alone or co-administered with 0.1 microg CT, or with 1 microg STE. All mice were boosted orally via gastric intubation 14 days after priming with 10 mg OVA alone, or co-administered with 10 microg CT or with 10 mg, 1 mg or 0.1 mg STE. One week later all mice were killed and organs obtained for analysis of the immune response. Intestinal, faecal and pulmonary OVA-specific sIgA concentration was significantly increased (p<0.05) in mice that received booster combinations of OVA/CT and OVA with all extract doses (p<0.05). Specific serum IgG titres did not differ significantly between groups. It is concluded that STE can significantly enhance secretory immunity in the intestine to OVA with mucosal homing to the lungs. The adjuvant effect of STE is comparable to that of CT.
  18. Abdul-Majeed S, Mohamed N, Soelaiman IN
    Life Sci, 2015 Mar 15;125:42-8.
    PMID: 25534439 DOI: 10.1016/j.lfs.2014.12.012
    Statins are competitive inhibitors of HMGCoA reductase and are commonly used as antihypercholesterolemic agents. Experimental studies clearly demonstrate the beneficial effects of statins on bone. Tocotrienols have also been shown to have anti-osteoporotic effects on the skeletal system. This study was conducted to observe the effect of a combination of delta-tocotrienol and lovastatin on structural bone histomorphometry and bone biomechanical strength in a postmenopausal rat model at clinically tolerable doses, and to compare it with the effect of delta-tocotrienol or lovastatin.
  19. Vyas T, Rapalli VK, Chellappan DK, Dua K, Dubey SK, Singhvi G
    Life Sci, 2021 Dec 15;287:120148.
    PMID: 34785190 DOI: 10.1016/j.lfs.2021.120148
    BACKGROUND: Biofilms are microcolonies of microbes that form communities with a variety of microbes, exhibit the same gene composition but differ in gene expression. Biofilm-associated infections have been in existence for a long, however, biofilm-associated skin disorders have not been investigated much.

    OBJECTIVES: Biofilms, which are made mostly of the matrix can be thought of as communities of microbes that are more virulent and more difficult to eradicate as compared to their planktonic counterparts. Currently, several formulations are available in the market which have the potential to treat biofilm-assisted skin disorders. However, the existing pharmacotherapies are not competent enough to cure them effectively and entirely, in several cases.

    KEY FINDINGS: Especially with the rising resistance towards antibiotics, it has become particularly challenging to ameliorate these disorders completely. The new approaches are being used to combat biofilm-associated skin disorders, some of them being photodynamic therapy, nanotherapies, and the use of novel drug delivery systems. The focus of attention, however, is nanotherapy. Micelles, solid lipid nanoparticles, quatsomes, and many others are being considered to find a better solution for the biofilm-associated skin disorders.

    SIGNIFICANCE: This review is an attempt to give a perspective on these new approaches for treating bacterial biofilms associated with skin disorders.

  20. Khalil ASM, Giribabu N, Yelumalai S, Shahzad H, Kilari EK, Salleh N
    Life Sci, 2021 Aug 01;278:119605.
    PMID: 33989665 DOI: 10.1016/j.lfs.2021.119605
    Diabetes mellitus (DM) may lead to testicular-related infertility while Myristic acid (MA) is beneficial to lower hyperglycaemia. Thus, we hypothesized that MA could protect testes against hyperglycaemia-induced damage in DM. DM was induced in adult male rats by high-fat diet consumption for 12 weeks, accompanied by a single dose streptozotocin injection. Following DM confirmation, the rats were fed orally with 10 and 20 mg/kg body weight MA for 28 consecutive days. After completion of treatment, rats were sacrificed and blood, cauda epididymis and testes were harvested. Serum was separated, epididymal sperm was collected for analysis. Molecular studies of the testes were performed by qPCR, Western blotting and immunostaining. MA was found to protect the testes against oxidative stress via preventing the upregulation of RAGE, Keap1, and the downregulation of Nrf2, NQO1, HO1, SOD, CAT and GPx. MA also prevented increase in testicular inflammation and apoptosis, as indicated by low inflammatory (NF-κB p65, IKKβ, TNF-α, IL-1β and iNOS) and apoptosis (Bax and caspase-9), but high anti-apoptosis (Bcl-2) markers' levels. Besides, MA prevented the downregulation of testicular steroidogenic markers (3βHSD, 17βHSD, StAR, ARA-54 and CYP11A1). Sperm analysis revealed near normal sperm count, motility, viability, lower abnormal sperm morphology in diabetic rats received MA. MA also prevented the loss of germ cells via preventing the decreased in cell proliferative marker (PCNA) while maintaining near normal epithelial height, tubular and Leydig cell diameters in the testes in DM. MA protects the testes against damage in DM, thus maintaining spermatogenesis and steroidogenesis, consequently preserving male fertility in diabetes.
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