Franciscus D. Suyatna

The Effects of Mangiferin (Mangifera indica L) in Doxorubicin-induced Cardiotoxicity in Rats.

AIM The cardiotoxicity effect of doxorubicin (DOX), a widely used antitumor agent has restricted its clinical application. The aim of the current study was to explore the potential protective effect of mangiferin, a naturally occurring glucosylxanthone, that have antioxidant activity by its iron-complexing ability in mitochondria, against DOX-induced cardiac toxicity in rats in comparison with other antioxidants namely Sylimarin (SYL) and Vitamin E (VitE). METHODS Mangiferin was given orally to rats at a dose of 50, and 100 mg/kg for 5 weeks, and DOX was injected at a total dose of 15 mg/kg. Cardiac toxicity was evaluated by lactate dehydrogenase and creatine kinase in the serum, malondialdehyde (MDA) level in plasma and cardiac tissue, and antioxidant enzyme superoxide dismutase (SOD) in cardiac tissue. RESULTS Mangiferin protected against DOX-induced increased mortality and electrocardiogram abnormality and decreased biochemical markers of cardiac toxicity i. e., lactate dehydrogenase and creatine phosphokinase isoenzyme. In addition, elevation of plasma and cardiac tissue levels of MDA in response to DOX treatment were significantly attenuated. The reduction of cardiac activity of SOD was significantly reduced in contrast with the other antioxidant SYL and Vit E. Histopathologically, mangiferin treatment showed significant reduction in inflammatory cell number, fibrotic area, and necrotic foci as compared with DOX only-treated rats. CONCLUSION These results suggested that mangiferin had better protective effect against DOX-induced cardiac toxicity in comparison with SYL and VitE, thus besides the antioxidant activity, different mechanism may be involved in the action of mangiferin and need to be clarified in the future studies.

Effect of Apium graveolens Extract Administration on the Pharmacokinetics of Captopril in the Plasma of Rats

Apium graveolens (celery) is an edible and traditionally medicinal plant that is used worldwide, among others for the treatment of hypertension. Combining celery with antihypertensive drugs can affect the pharmacodynamics and pharmacokinetics of the latter drugs. The aim of the study is to assess the effects of administrating the celery extract on captopril pharmacokinetics. Sprague-Dawley strain rats were divided into two groups (n = 6). Group I was given captopril (10 mg/kg Body Weight (BW)) orally, while Group II was pretreated with celery extract orally (40 mg/kg BW) an hour before administration of captopril. The blood samples were withdrawn at various intervals after drug administration. The captopril concentration was determined using liquid chromatography–mass spectrometry (LC-MS/MS) and from the blood data, the values of Ke, Cmax, Tmax, T1/2, and area under the curve (AUC) were calculated. The results showed that oral administration of the celery extract increased Cmax (38.67%), T1/2 (37.84%), and AUC (58.10%) and decreased Ke (27.45%) of captopril in Group II (celery + captopril) compared with Group I (captopril). In conclusion, celery extract can alter the pharmacokinetic of captopril when given in combination. The combination might be beneficial for the treatment of hypertension, as celery causes an increase in the plasma level of captopril, which can enhance its efficacy.

Neuroglobin correlates with cryptochrome-1 in obstructive sleep apnea with primary aldosteronism

Background Neuroglobin (Ngb) is highly expressed in the suprachiasmatic nucleus, and can regulate Per1 gene expression. It is still not known whether Ngb also influences Cryptochrome (Cry). Cry is implicated in hypertension and primary aldosteronism (PA) in mice. There is a strong correlation between Obstructive Sleep Apnea (OSA) and PA. We propose to prove that Ngb and Cry play a role in OSA with PA. Methods Subjects were recruited consecutively from residents of Jakarta, Indonesia; subjects aged 30–65 years with moderate to severe OSA and hypertension were included in the study. OSA was diagnosed using an unattended type 2 portable monitor (Alice Pdx), hypertension was diagnosed when morning blood pressure exceeded 140/90 mmHg or when taking anti-hypertensive drugs. Serum concentration of aldosterone, renin, Cry1, Cry2 and Ngb protein were determined using ELISA method. Primary aldosteronism (PA) was defined as ARR ≥20. Results Forty subjects were recruited, 26 male and 14 female, median age 52.5 years, BMI 27.46 kg/m2, and AHI 34.8 times/hour. We found 16 subjects with PA and 24 non PA. Cry1 and Cry2 did not correlate with ARR in PA and non PA groups. Ngb correlated positively with Cry1 (Spearman’s rho = 0.455, p = 0.038) but not Cry2 in PA patients. Cry1 concentration decreased in severe hypoxia. Conclusions Ngb correlates with Cry1 in OSA with PA. There is no correlation between Cry1 or Cry2 with PA

Anti-Diabetic Potential of Murraya Koenigii (L.) and its Antioxidant Capacity in Nicotinamide-Streptozotocin Induced Diabetic Rats

AIM AND OBJECTIVE The present study aims to investigate whether the antihyperglycemic effect of Murraya koenigii is mediated by antioxidant properties and insulin mimetic effect. METHODS Thirty Spraque-Dawley rats were induced hyperglycemia by streptozotocin and nicotinamide (STZ-NA). The STZ-NA diabetic rats were treated with an ethanolic extract of Murraya koenigii 200 mg/kg b.w and 400 mg/kg b.w. One group was treated with glibenclamide (1 mg/kg b.w). After the administration of Murraya koenigii extract and glibenclamide for four weeks, the rats were sacrificed. Blood and organ samples were collected under a fasting condition. The body weight and blood glucose levels were measured. Hepatic enzymes were determined using a commercial kit, protein levels were estimated by Bradfords method, and plasma insulin was assayed by an ELISA kit. Malondialdehyde (MDA) and reduced glutathione (GSH) levels were estimated by the TBA-Wills method and Ellmans method, respectively. RESULTS Ethanolic extract of Murraya koenigii showed a significant reduction in blood glucose level at both doses, 200 and 400 mg/kg b.w. In addition, Murraya koenigii exhibited a profound antioxidant effect with decreased MDA level and increased GSH level, particularly at the 200 mg/kg b.w. and significantly decreased the HOMA-IR index. CONCLUSIONS The present study reveals that Murraya koenigii possesses antidiabetic activity and antioxidant effects on STZ-NA induced diabetes mellitus.

Association of the HLA-B alleles with carbamazepine-induced Stevens–Johnson syndrome/toxic epidermal necrolysis in the Javanese and Sundanese population of Indonesia: the important role of the HLA-B75 serotype

Carbamazepine (CBZ) is a common cause of life-threatening cutaneous adverse drug reactions such as Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Previous studies have reported a strong association between the HLA genotype and CBZ-induced SJS/TEN. We investigated the association between the HLA genotype and CBZ-induced SJS/TEN in Javanese and Sundanese patients in Indonesia. Nine unrelated patients with CBZ-induced SJS/TEN and 236 healthy Javanese and Sundanese controls were genotyped for HLA-B and their allele frequencies were compared. The HLA-B*15:02 allele was found in 66.7% of the patients with CBZ-induced SJS/TEN, but only in 29.4% of tolerant control (p = 0.029; odds ratio [OR]: 6.5; 95% CI: 1.2–33.57) and 22.9% of healthy controls (p = 0.0021; OR: 6.78; 95% CI: 1.96–23.38). These findings support the involvement of HLA-B*15:02 in CBZ-induced SJS/TEN reported in other Asian populations. Interestingly, we also observed the presence of the HLA-B*15:21 allele. HLA-B*15:02 and HLA-B*15:21 are members of the HLA-B75 serotype, for which a greater frequency was observed in CBZ-induced SJS/TEN (vs tolerant control [p = 0.0078; OR: 12; 95% CI: 1.90–75.72] and vs normal control [p = 0.0018; OR: 8.56; 95% CI: 1.83–40]). Our findings suggest that screening for the HLA-B75 serotype can predict the risk of CBZ-induced SJS/TEN more accurately than screening for a specific allele.

Antiviral Effect of Sub Fraction Cassia alata Leaves Extract to Dengue Virus Serotype-2 strain New Guinea C in Human Cell Line Huh-7 it-1

Dengue virus (DENV) is one of the most common viral infections found Indonesia and tropical regions, and no specific antiviral for DENV. Indonesia has several of herbal medicine that were not explored of their potency as antiviral DENV. This study was done to evaluate the activity and toxicity of 4 derived fractions: Hexane (CA1), ethyl acetate (CA2), buthanol (CA3 ) and water (CA4) of Cassia alata leaf extract (CA) as an antiviral drug to DENV. The DENV was treated with various concentration of extract and added to Huh-7 it-1. The decrease of virus titer was determined by Focus assay. The toxicity of extract was measured by MTT assay. In our previous study, we found that CA on Huh-7 cells showed IC50, CC50 and SI values of <10 μg/mL, 323.45 μg/mL, and more than 32.3, respectively. For the fractions, CA3 showed best antiviral activity among other, with IC50, CC50 and SI of <10 μg/mL, 645.8 μg/mL, and more than 64.5, respectively. CA and CA3 were proven to possess antiviral activity that is potent when tested against DENV-2. Future study was needed to explore the inhibition mechanism and compound of CA that have potency as antiviral drug to DENV.