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  1. Thanapairoje K, Junsiritrakhoon S, Wichaiyo S, Osman MA, Supharattanasitthi W
    J Basic Clin Physiol Pharmacol, 2023 May 01;34(3):277-289.
    PMID: 36631934 DOI: 10.1515/jbcpp-2022-0242
    Ageing is the process generated by senescent cells, free radicals, inflammation and other relevant factors. Ageing contributes to age-related diseases that affect the quality of life. People are interested in anti-ageing intervention and many scientists attempt to search for anti-ageing medicines. This review focused on describing in vivo anti-ageing activity of US-FDA-approved drugs and found that alogliptin, canagliflozin and metformin might produce anti-ageing activity via AMPK activation. Rapamycin and canagliflozin are capable to inhibit mTOR to promote lifespan. Atracurium, carnitine and statins act as DAF-16 activators, which potentially contribute to anti-ageing activity. Hydralazine, lisinopril, rosiglitazone and zidovudine may help stabilize genomic integrity to prolong life expectancy. Other indirect mechanisms, including insulin-lowering effect by acarbose and calcium channel blocking activity by verapamil may also promote longevity. Interestingly, some drugs (i.e., canagliflozin, metformin, rapamycin and acarbose) are likely to demonstrate a lifespan-promoting effect predominantly in male animals. These pre-clinical data might provide mechanistic and phenotypic perspectives to better understand the targets of anti-ageing interventions.
  2. Rejeki PS, Baskara PG, Herawati L, Pranoto A, Setiawan HK, Lesmana R, et al.
    J Basic Clin Physiol Pharmacol, 2022 Nov 01;33(6):769-777.
    PMID: 35286051 DOI: 10.1515/jbcpp-2021-0393
    OBJECTIVES: Positive energy homeostasis due to overnutrition and a sedentary lifestyle triggers obesity. Obesity has a close relationship with elevated levels of betatrophin and may increase the risk of developing metabolic syndrome. Therefore, lifestyle modification through a nonpharmacological approach based on physical exercise is the right strategy in lowering betatrophin levels. This study aimed to analyze the effect of moderate-intensity interval and continuous exercises on decreased betatrophin levels and the association between betatrophin levels and obesity markers in women.

    METHODS: A total of 30 women aged 20-24 years old were randomly divided into three groups. Measurement of betatrophin levels using Enzyme-Linked Immunosorbent Assay (ELISA). Data analysis techniques used were one-way ANOVA and parametric linear correlation.

    RESULTS: The results showed that the average levels of betatrophin pre-exercise were 200.40 ± 11.03 pg/mL at CON, 203.07 ± 42.48 pg/mL at MIE, 196.62 ± 21.29 pg/mL at MCE, and p=0.978. Average levels of betatrophin post-exercise were 226.65 ± 18.96 pg/mL at CON, 109.31 ± 11.23 pg/mL at MIE, 52.38 ± 8.18 pg/mL at MCE, and p=0.000. Pre-exercise betatrophin levels were positively correlated with age, BMI, FM, WHR, FBG, and PBF (p≤0.001).

    CONCLUSIONS: Our study showed that betatrophin levels are decreased by 10 min post-MIE and post-MCE. However, moderate-intensity continuous exercise is more effective in lowering betatrophin levels than moderate-intensity interval exercise. In addition, pre-exercise betatrophin levels also have a positive correlation with obesity markers.

  3. Rejeki PS, Witarto BS, Witarto AP, Rifdah SN, Wafa IA, Utami DM, et al.
    J Basic Clin Physiol Pharmacol, 2023 May 01;34(3):311-320.
    PMID: 36957989 DOI: 10.1515/jbcpp-2023-0040
    Moderate-to-vigorous physical activity (MVPA) has been shown to have a favorable effect on many diseases as a complementary therapy and is a critical component of healthy living. During the pandemic era, physical activity has been promoted for resistance against coronavirus disease 2019 (COVID-19). However, there is scarce evidence on whether MVPA could reduce the infectivity and susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The objective of this meta-analysis was to determine the effect of MVPA on morbidity, mortality, and duration of hospitalization in COVID-19 patients. We performed a comprehensive search of five online databases for eligible studies up to September 9, 2021. Meta-analyses were conducted to determine the association between MVPA and COVID-19-related morbidity, hospitalization, and mortality. The odds ratio (OR) was applied as the summary statistic for the primary outcomes. Secondary analyses were conducted to evaluate the difference in the metabolic equivalent of tasks (METs) between the outcome and non-outcome groups with the mean difference as the pooled effect. This meta-analysis included eight observational studies. We found that MVPA significantly reduced the odds of contracting SARS-CoV-2 infection (OR=0.88; 95% confidence interval [CI] = 0.85-0.92), hospitalization (OR=0.56; 95% CI=0.35-0.92), and mortality (OR=0.42; 95% CI=0.21-0.81) due to COVID-19 compared to no physical activity. METs≥500 min/week were linked to decreased morbidity and mortality of COVID-19 (OR=0.94 [95% CI=0.90-0.98]; OR=0.56 [95% CI=0.38-0.83]). COVID-19 patients with MVPA demonstrated a lower risk of COVID-19-related morbidity, hospitalization, and mortality compared to those who were less active, highlighting the importance of an active lifestyle despite the pandemic situation where such activities are limited.
  4. Noh MAA, Fazalul Rahiman SS, A Wahab H, Mohd Gazzali A
    J Basic Clin Physiol Pharmacol, 2021 Jun 25;32(4):715-722.
    PMID: 34214294 DOI: 10.1515/jbcpp-2020-0435
    OBJECTIVES: Tuberculosis (TB) remains a public health concern due to the emergence and evolution of multidrug-resistant strains. To overcome this issue, reinforcing the effectiveness of first line antituberculosis agents using targeted drug delivery approach is an option. Glyceraldehyde-3-Phosphate Dehydrogenase (GADPH), a common virulence factor found in the pathogenic microorganisms has recently been discovered on the cell-surface of Mycobacterium tuberculosis, allowing it to be used as a drug target for TB. This study aims to discover active small molecule(s) that target GAPDH and eventually enhance the delivery of antituberculosis drugs.

    METHODS: Ten ligands with reported in vitro and/or in vivo activities against GAPDH were evaluated for their binding interactions through molecular docking studies using AutoDock 4.2 program. The ligand with the best binding energy was then modified to produce 10 derivatives, which were redocked against GAPDH using previous protocols. BIOVIA Discovery Studio Visualizer 2019 was used to explore the ligand-receptor interactions between the derivatives and GAPDH.

    RESULTS: Among the 10 ligands, curcumin, koningic acid and folic acid showed the best binding energies. Further analysis on the docking of two folic acid derivatives, F7 (γ-{[tert-butyl-N-(6-aminohexyl)]carbamate}folic acid) and F8 (folic acid N-hydroxysuccinimide ester) showed that the addition of a bulky substituent at the carboxyl group of the glutamic acid subcomponent resulted in improved binding energy.

    CONCLUSIONS: Folic acid and the two derivatives F7 and F8 have huge potentials to be developed as targeting agents against the GAPDH receptor. Further study is currently on-going to evaluate the effectiveness of these molecules in vitro.

  5. Mohd Nasir NA, Agarwal R, Krasilnikova A, Sheikh Abdul Kadir SH, Iezhitsa I
    J Basic Clin Physiol Pharmacol, 2020 Jul 22;31(6).
    PMID: 32697755 DOI: 10.1515/jbcpp-2019-0373
    Objectives Steroid-induced ocular hypertension and glaucoma are associated with extracellular matrix remodeling at the trabecular meshwork (TM) of the eye due to reduced secretion of matrix metalloproteinases (MMPs), a family of enzymes regulating extracellular matrix proteolysis. Several biological functions of steroids are known to involve regulation of adenosine A1 receptors (A1AR) and nuclear factor kappa B (NFKB). Since MMPs expression in TM has been shown to be regulated by A1AR as well as transcription factors, it is likely that dexamethasone-induced changes in aqueous humor dynamics involve reduced MMP and A1AR expression and reduced NFKB activation. Hence, the current study investigated the association of dexamethasone-induced reduction in MMP secretion with reduced NFKB activation and A1AR expression. Methods Human trabecular meshwork cells (HTMCs) were characterized by estimating myocilin and alpha smooth muscle actin expression and then were treated with dexamethasone 100 nM for 2, 5 and 7 days. The MMP secretion was estimated in culture media using Western blot. Immunocytochemistry (ICC) and ELISA were done to investigate the effect of dexamethasone on NFKB phosphorylation. A1AR expression in HTMCs was determined using Western blot and ELISA. Results Dexamethasone caused a significant reduction in both MMP-2 and -9 expression compared to untreated group after five and seven days but not after two days of culture. Significantly reduced phosphorylated NFKB and A1AR protein levels were detected in dexamethasone treated compared to vehicle treated HTMCs after five days of culture. Conclusions Dexamethasone reduces MMP-2 and -9 secretion by HTMCs and this effect of dexamethasone is associated with reduced NFKB phosphorylation and A1AR expression.
  6. Loh KW, Shaz N, Singh S, Malliga Raman M, Balaji Raghavendran HR, Kamarul T
    J Basic Clin Physiol Pharmacol, 2023 Mar 01;34(2):177-185.
    PMID: 34182614 DOI: 10.1515/jbcpp-2020-0320
    OBJECTIVES: Primary Osteoarthritis (OA) is a disease of progressive joints degeneration due to idiopathic causes. Recent evidence showed a positive relationship between OA and metabolic syndrome. This pilot study aimed to assess the baseline level of pro and anti-inflammatory cytokines in OA patients with or without Diabetic Mellitus (DM) and assess the effect of hydrogen peroxide (H2O2) in cytokine production.

    METHODS: Patients with primary hip and knee OA were recruited, and 3 mL of bone marrow was harvested during joint replacement surgery. Bone marrow stromal cells (BMSC) was isolated and cultured in a culture flask for three passages. Later experiment was then sub-cultured in a well plate labeled as the control group and H2O2 (0.1 mM) treated group. ProcartaPlex® Multiplex Immunoassay was performed to measure cytokine levels produced by the BMSC at 0 h, as well as 72 h.

    RESULTS: Cytokines such as tumor necrosis factor-alpha, interleukin (IL)-6, IL-8, and IL-1β generally exhibited higher cytokine levels in subjects with DM than in nonDM subjects at 0 and 72 h. For IL-17, its expression was similar in nonDM and DM groups at 0 and 72 h. Cytokine IL-10 showed no significant difference in both the groups while DM and nonDM groups treated with H2O2 showed decreased IL-4 levels compared to control groups at 72 h. Bone marrow cells from DM-OA are more vulnerable to chemical insult and are associated with higher levels of proinflammatory cytokines production and lower IL-4 level production.

    CONCLUSIONS: This study provides a clue that management of OA with co-morbidity like DM needs future studies.

  7. Jegasothy R, Sengupta P, Dutta S, Jeganathan R
    J Basic Clin Physiol Pharmacol, 2020 Dec 14;32(5):911-924.
    PMID: 33580644 DOI: 10.1515/jbcpp-2020-0236
    Climate change is an incessant global phenomenon and has turned contentious in the present century. Malaysia, a developing Asian country, has also undergone significant vicissitudes in climate, which has been projected with significant deviations in forthcoming decades. As per the available studies, climate changes may impact on the fertility, either via direct effects on the gonadal functions and neuroendocrine regulations or via several indirect effects on health, socioeconomic status, demeaning the quality of food and water. Malaysia is already observing a declining trend in the Total fertility rate (TFR) over the past few decades and is currently recorded below the replacement level of 2.1 which is insufficient to replace the present population. Moreover, climate changes reportedly play a role in the emergence and cessation of various infectious diseases. Besides its immediate effects, the long-term effects on health and fertility await to be unveiled. Despite the huge magnitude of the repercussion of climate changes in Malaysia, research that can explain the exact cause of the present reduction in fertility parameters in Malaysia or any measures to preserve the national population is surprisingly very scarce. Thus, the present review aims to elucidate the possible missing links by which climate changes are impairing fertility status in Malaysia.
  8. Ang HH, Lee KL, Kiyoshi M
    PMID: 14964739 DOI: 10.1515/jbcpp.2003.14.3.301
    Eurycoma longifolia Jack was investigated for sexual motivation activity in adult, middle-aged male mice and in retired breeders, using the modified open field and the modified runway choice methods. Each mouse received 500 mg/kg of one of 4 fractions of E. longifolia Jack, viz. chloroform, methanol, butanol, and water, whereas the mice in the control and yohimbine groups received 3 ml/kg of normal saline and 30 mg/kg of yohimbine daily respectively for 10 d. The results show a transient increase in the percentage of male mice responding to the right choice after chronic consumption of the fractions with 50 percent of the adult middle-aged male mice treated with E. longifolia Jack and yohimbine scoring the right choice after 8 and 5 days post-treatment respectively. In conclusion, this study has shown that E. longifolia Jack continues to enhance sexual motivation in adult, middle-aged male mice and in retired breeders.
  9. Ang HH, Lee KL, Kiyoshi M
    J Basic Clin Physiol Pharmacol, 2004;15(3-4):303-9.
    PMID: 15803965 DOI: 10.1515/jbcpp.2004.15.3-4.303
    Eurycoma longifolia Jack commonly known as Tongkat Ali in Malaysia, has been used in Malaysia to increase male virility and sexual prowess. The objective of this study is to evaluate sexual arousal in sexually sluggish old male rats, 24 months old and retired breeders, receiving 200, 400, or 800 mg/kg of various fractions of E. longifolia Jack, twice daily, for 10 days. Control rats received 3 ml/kg of normal saline. The aphrodisiac effect was monitored by the act of yawning and stretching because yawning, either alone or associated with stretching, is considered an ancestral vestige surviving throughout evolution that promotes sexual arousal. The results showed that 800 mg/kg of E. longifolia Jack increased yawning by 50% and stretching by 16.7% in sexually sluggish old male rats, by 676-719% and 31-336%, respectively, in sexually active male rats, and by 22-44% and 75-100%, respectively, in middle aged, 9 months old and retired breeders. We conclude that the results of this study support the folk use of this plant as an aphrodisiac.
  10. Ang HH, Lee KL
    J Basic Clin Physiol Pharmacol, 2002;13(3):249-54.
    PMID: 12670032 DOI: 10.1515/jbcpp.2002.13.3.249
    The effect of increasing doses of various fractions of Eurycoma longifolia Jack extracts on libido was examined in middle-aged male rats. The results showed that a high dose (800 mg/kg) of all E. longifolia Jack extracts significantly increased mount frequency (MF) (P < 0.05) over that of untreated controls, but had no effect on the frequency of intromission or ejaculation. Methanol, chloroform, water, and butanol fractions exhibited MF of 2.5 +/- 0.1, 2.6 +/- 0.3, 2.5 +/- 0.1 and 2.6 +/- 0.2, respectively, in adult, middle-aged male rats, and retired breeders versus 2.3 +/- 0.1 in untreated controls. This translated to a minor increase in MF of 8.7%, 13.0%, 8.7%, and 13.0% for these fractions, respectively, during the 20-minute observation period. The results of this study show that E. longifolia Jack extracts can increase libido in middle-aged male rats.
  11. Abidin AZ, Rosli NS, Segaran S, Jasni AS, Bahari H
    J Basic Clin Physiol Pharmacol, 2021 Feb 08;32(6):1047-1055.
    PMID: 33544993 DOI: 10.1515/jbcpp-2020-0053
    OBJECTIVES: Pre-pregnancy obesity is a serious epidemics concern that negatively affects the neurodevelopmental of the offspring. Elateriospermum tapos (E. tapos) commonly used to enhance weight loss in obesity treatment. This study was aimed to investigate the influence of E. tapos supplement in obese maternal prior pregnancy on the offspring's bodyweight, lipid metabolism and memory function.

    METHODS: Thirty female Sprague Dawley rats were used. Six rats were assigned to the normal diet group (DND). The remaining rats were fed with a high-fat and cafeteria diet (HFCD) to generate obesity for 5 weeks. Obese rats were further divided into four groups: Negative Control (DNC; HFCD), Positive Control (DPC; Orlistat 200 mg/kg), treatment 1 (DTX1; E. tapos seed 200 mg/kg) and treatment 2 (DTX2, E. tapos shell 200 mg/kg) were given daily, for 6 weeks prior to mating. At weaning, offspring of both genders were designated into six groups according to their dam's group (n=6/group). All groups were fed with a cafeteria diet except for the control group. Memory tasks for object and place recognition were conducted on offspring at eighth weeks of age. The offspring were cull at the 12th week of age for their blood sample.

    RESULTS: Both offspring genders from DTX2 significantly reduce bodyweight, calorie intake and triglyceride level. In memory tasks, offspring from DTX2 showed a significant increase in exploration rate in place test as compared to offspring from the DNC group.

    CONCLUSIONS: This study highlights E. tapos shell as an anti-obesity agent and protecting memory deficit in obese dam's offspring.

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