Comparative Neuroprotective Effects of Moringa oleifera Seed Oil and Aqueous Extract on Cognitive Functions on a High-Fat, High-Fructose Diet Mice: Focus on Senescence Markers.

Several studies have demonstrated that Moringa oleifera (MO) has different pharmacological properties, including neuroprotective effects. However, the role of MO in preventing brain impairment in high-fat, high-fructose diet (HFFD) remains unknown. This study aimed to investigate the neuroprotective effects of MO leaves aqueous extract (MOE) and moringa seed oil (MOO) against brain impairment in mice with HFFD. Twenty-eight male mice were randomly divided into four groups: normal diet, HFFD, HFFD + MOE 500 mg/kgBW, and HFFD + MOO 2 mL/kgBW. Cognitive function was assessed using the Y-maze and novel object recognition (NOR) tests. The p16, p21, and BDNF expressions were analyzed using the RT-PCR method. Senescence-associated beta-galactosidase (SA-ß-gal) staining in the brain was also performed. The results showed that administration of MOE or MOO could increase the percentage of alternation and recognition of new objects, prevent the increase of p16 and p21 expression, and ameliorate SA-ß-Gal activity in the brain. MOO, but not MOE, increased BDNF expression in senescence brains isolated from HFFD mice. The findings indicate that MOO and MOE possess neuroprotective properties, with MOO demonstrating a greater ability to inhibit the brain senescence process compared to MOE.

Hypolipidemic effect of brown seaweed (Sargassum crassifolium) extract in vivo (Study of histopathology, mRNA expression, and immunohistochemistry (IHC) with VCAM-1, ICAM-1, and MCP-1 parameters).

The purpose of this study was to obtain natural drugs from brown seaweed (Sargassum crassifolium) as antiatherosclerosis candidates through the study of hypolipidemic mechanisms of action. Modeling of dyslipidemia rats was carried out by feeding high-fat (HFF) and doses of crude fucoidan 100. 200. 400mg / KgBB. in both treatments measured blood lipid profile levels taken from the orbital sinuses. HE's histopathology. mRNA expression. immunohistochemistry (IHC) with parameters VCAM-1. ICAM-1. and MCP-1 were performed on adipose tissue. as well as liver. Total cholesterol values 51.07-225.2. triglycerides 30.43-115.73. HDL 13.1-24.86 mg/dl and LDL 20.22-189.68 mg/dl. In the treatment of crude fucoidan obtained the result of p value < α (0.05. Histopathological features of adipose tissue after administration of HFF for 60 days resulted in an increase in adipose cell size. and the liver experienced structural damage and inflammation. but after 21 days of treatment the morphological picture of adipose tissue was similar to normal morphology and the liver also decreased in severity and inflammation. The results of histochemical staining after treatment showed a positive staining part on MCP-1. The result of p value < α (0.05) of mRNA expression for administration of 3 treatment doses. A dyslipidemic mouse model with HFF administration for 60 days succeeded in becoming a dyslipidemic rat. and crude fucoidan had hypolipidemic activity. Doses of 100. 200. and 400 mg/KgBB crude fucoidan showed improvement in adipose and liver morphological features of severity and inflammation of dyslipidemic rats and decreased mRNA expression.

Moringa oleifera Leaves Extract Ameliorates Doxorubicin-Induced Cardiotoxicity via Its Mitochondrial Biogenesis Modulatory Activity in Rats.

Background: Doxorubicin, an anthracycline class of anticancer, is an effective chemotherapeutic agent with serious adverse effects, mainly cardiotoxicity. Several possible causes of doxorubicin cardiotoxicity are increased oxidative stress, nucleic acid and protein synthesis inhibition, cardiomyocyte apoptosis, and mitochondrial biogenesis disruptions. Moringa oleifera (MO), a naturally derived medicine, is known for its antioxidative properties and activity in alleviating mitochondrial dysfunction. To determine the potency and possible cardioprotective mechanism of MO leaves aqueous extract via the mitochondrial biogenesis pathway in doxorubicin-induced rats. Methods: Twenty-four Sprague-Dawley rats were divided into four groups of six. The first group was normal rats; the second group was treated with doxorubicin 4 mg/kg BW intraperitoneally once weekly for four weeks; the third and fourth groups were treated with doxorubicin 4 mg/kg BW intraperitoneally once weekly, and MO leaves extract at 200 mg/kg BW or 400 mg/kg BW orally daily, for four weeks. At the end of the fourth week, blood and cardiac tissues were obtained and analyzed for cardiac biomarkers, mitochondrial DNA copy number, mRNA expressions of peroxisome-activated receptor-gamma coactivator-1 alpha (PGC-1α), the nuclear factor erythroid 2-related factor 2 (Nrf2), superoxide dismutase 2 (SOD2), caspase 3, the activity of glutathione peroxidase (GPx), levels of 8-hydroxy-2-deoxyguanosine (8-OH-dG), and malondialdehyde. Results: MO leaves extract was shown to decrease biomarkers of cardiac damage (LDH and CK-MB), malondialdehyde levels, and GPx activity. These changes align with the reduction of mRNA expressions of caspase-3, the increase of mRNA expressions of PGC-1α and Nrf2, and the elevation of mitochondrial DNA copy number. MO leaves extracts did not influence the mRNA expressions of superoxide dismutase 2 (SOD2) or the levels of 8-OH-dG. Conclusion: Moringa oleifera leaves extract ameliorates doxorubicin-induced cardiotoxicity by reducing apoptosis and restoring gene expression of PGC-1α and Nrf2, a key regulator in mitochondrial biogenesis.

The efficacy and safety of first-line anti-seizure medications as substitution therapy for children with drug-resistant epilepsy: a randomized controlled trial protocol.

Although many anti-seizure medications (ASMs) are available, treatment failure, known as drug-resistant epilepsy (DRE), still occurs in around 30% of children with epilepsy. Second-line ASMs are usually used as substitution therapy in DRE to control seizures, although international consensus is not available yet. Previous studies focus on comparing the ASMs, whether as add-on or substitution therapy, mainly conducted in newly diagnosed epilepsy. However, the study that investigated first-line ASMs as substitution therapy compared to second-line ones, particularly among DRE children, is still lacking. A randomized controlled trial (RCT) enrolling 102 participants, aged 1-18, at three referral hospitals in Indonesia will be conducted, dividing them into intervention and control groups. The intervention group will be treated with first-line ASMs as the substitution therapy, while the other in the control group will get second-line ASMs. The primary outcome measure is the proportion difference of responders between groups who get first-line and second-line ASMs in 14 weeks of intervention. Clinical trial registration: ClinicalTrials.gov, identifier NCT05697614.

Effect of Roselle Flower Extract (Hibiscus sabdariffa Linn.) on Reducing Steatosis and Steatohepatitis in Vitamin B12 Deficiency Rat Model.

Background and Objectives: Non-alcoholic Fatty Liver Disease (NAFLD) can occur as a result of micronutrient deficiencies. Hibiscus sabdarifa, a plant used in traditional medicine, contains ingredients that can help prevent this process. This study looked at the potency of Hibiscus sabdariffa Ethanol Extract (HSE) to prevent homocysteine-induced liver damage in animals that were deficient in vitamin B12. Materials and Methods: A comparative study of the effects of roselle extract is presented in an experimental design. Thirty Sprague-Dawley rats were divided into six groups using randomization. To demonstrate the absence of liver damage in the experimental animals under normal conditions, a control group was fed a normal diet without HSE. For the induction of liver damage in the experimental animals, the vitamin B12-restricted group was administered a vitamin B12-restricted diet. To test the effect of HSE on liver damage, the treatment group was given HSE along with a vitamin B12-restricted diet. Each group was given two treatment periods of eight and sixteen weeks. These results were compared with the results of the parameter examination between the vitamin B12 restriction group, with and without HSE, using an ANOVA statistic. The data were analyzed with licensed SPSS 20.0 software. Results: HSE significantly increased the blood levels of vitamin B12 while lowering homocysteine levels. The administration of HSE reduced liver damage based on the activity of liver function enzymes in the plasma due to a limitation of vitamin B12. HSE decreased Sterol Regulatory Element-Binding Protein-1c (SREBP1c) and Nuclear Factor Kappa B (NFkB) protein expressions in the liver tissue, but did not decrease Glucose-Regulated Protein 78 (GRP78) protein expression. Significantly, the levels of Tumor Necrosis Factor alpha (TNF-a) and IL-6 in the liver tissue were lower, while the levels of IL-10 and Nuclear factor-erythroid-2 Related Factor 2 (NRF2) were higher with HSE administration. HSE produced a better histopathological profile of the Hematoxylin and Eosin (H&E)-Masson tricrome for inflammation, fat and fibrosis in the liver. Conclusions: In this study, HSE was found to slow the development of liver damage in experimental animals that were given a vitamin B12-deficient diet.

Nanocurcumin preserves kidney function and haematology parameters in DMBA-induced ovarian cancer treated with cisplatin via its antioxidative and anti-inflammatory effect in rats.

CONTEXT: Cisplatin, as a first-line treatment for ovarian cancer, is associated with debilitating adverse effects, including nephrotoxic and haematotoxic effects. OBJECTIVE: This study determines whether nanocurcumin, combined with cisplatin, would give additional benefit to kidney function and haematological parameters in rats with ovarian cancer. MATERIALS AND METHODS: Twenty-five Wistar rats were divided into five untreated rats and 20-dimethylbenz(a)anthracene (DMBA)-induced ovarian cancer rats. The 20 ovarian cancer rats were divided into four treatment groups: vehicle, cisplatin, cisplatin-curcumin, and cisplatin-nanocurcumin. Cisplatin was given at the dose of 4 mg/kg BW once weekly, while curcumin or nanocurcumin was administered at 100 mg/kg BW daily for four weeks. At the end of treatment, we analysed kidney function, haematological parameters, and inflammatory and oxidative stress markers from plasma. RESULTS: Nanocurcumin alleviates the increase in kidney function markers and abnormalities in haematological indices in rats treated with cisplatin. Compared to cisplatin-treated rats, plasma urea levels decreased from 66.4 to 47.7 mg/dL, creatinine levels lowered from 0.87 to 0.82 mg/dL, and neutrophil gelatinase-associated lipocalin (NGAL) levels declined from 8.51 to 3.59 mIU/mg protein. Furthermore, the therapy increased glutathione activities (from 2.02 to 3.23 U/µL), reduced lipid peroxidation (from 0.54 to 0.45 nmol/mL), and decreased plasma TNF-α (from 270.6 to 217.8 pg/mL). CONCLUSIONS: Cisplatin with nanocurcumin in an ovarian cancer rat model may provide additional benefits as a preventive agent against renal impairment and cisplatin-induced haematological toxicity. However, further research is required to prove that using nanocurcumin for a more extended time would not affect its anticancer properties.

The Oil Formulation Derived from Moringa Oleifera Seeds Ameliorates Behavioral Abnormalities in Water-immersion Restraint Stress Mouse Model.

Purpose: Repeated stress events are well known to be associated with the onset of behavioral abnormalities including depression, anxiety and memory impairment. In spite of the traditional uses of Moringa oleifera (MO), no experimental evidence for its use against chronic stress exists. Here, we investigated whether seed oil from MO (MOO) could improve behavior abnormalities of chronic stress mice induced by water-immersion restraint stress (WIRS) and the underlying mechanism. Methods: BALB/C male mice at 12 weeks of age were exposed to chronic WIRS for two weeks and divided in to four groups: normal group, WIRS group, WIRS+MOO1 group (treated with MOO at the dose of 1 mL/kg BW), and WIRS+MOO2 group (treated with MOO 2 mL/kg BW). The MOO treatment was given orally for 23 days. On day 24, we checked the behavior parameters, the plasma level of cortisol, acetylcholinesterase (AChE) activity in hippocampus, mRNA expression level of brain-derived neurotrophic factor (BDNF) and oxidative stress parameters in brain tissues. In addition, we also checked the histopathological features of the gastric mucosa wall. Results: Administration of MOO ameliorated anxiety-like, depression-like and memory impairment phenotypes in the WIRS mouse model although the plasma cortisol concentrations were comparable among the groups. Of note, MOO both in two doses could suppress the AChE activity in hippocampus tissue and ameliorated the MDA level in prefrontal cortex tissue in mice exposed to WIRS. Although only WIRS+MOO2 group could increase the mRNA expression of BDNF, the histopathological gastric mucosa wall features were improved in all MOO groups. Conclusion: Taken together, these finding suggested that MOO may have a neuroprotective effect in the mouse model of WIRS as evidenced by improving the abnormal behaviors through enhancing mRNA expression level of BDNF, inhibited AChE activity, and prevented the increase of MDA level in the brain.

Protective effects of silver nanoparticles in isoproterenol-induced myocardial infarction in rats.

Background: Silver nanoparticles (AgNPs) are widely used in the medical field, including cardiovascular. However, limited research has investigated the effect of AgNPs on the protection of myocardial infarction (MI). Objectives: Isoproterenol (Iso)-induced MI and the cardiac protection offered by AgNPs were investigated in the present study. Additionally, we characterized the profile of Ag in the form of nanoparticles. Methods: Twenty-four male Wistar rats were randomly divided into four groups as follows: normal, Iso, Iso + AgNO3, and Iso + AgNP groups. AgNPs and silver ion (AgNO3) were administered intraperitoneally at 2.5 mg/kg BW for 14 days. Iso induction was performed using two doses of 85 mg/kg BW given subcutaneously on days 13 and 14. Blood and cardiac tissue samples were taken 24 h after the last dose of Iso and checked for Creatine Kinase-MB (CK-MB), lactate dehydrogenase in plasma along with oxidative stress parameters, mitochondria biogenesis markers, and inflammation representative genes in cardiac tissue. Additionally, we analyzed the histopathological features in cardiac tissue. Results: The silver was confirmed in the form of nanoparticles by its size at intervals of 8.72-37.84 nm. Both AgNO3 and AgNPs showed similar cardioprotective effects, as shown by the decrease in biochemical markers of cardiac toxicity, namely, CK-MB. Additionally, AgNPs group have better efficacy compared with AgNO3 group in ameliorating Iso-mediated oxidative stress production, as evidenced by the significant decrease in malondialdehyde level and increased superoxide dismutase activity (P < 0.0001 and P < 0.01, respectively) in cardiac tissue compared with the Iso group. Mechanistically, AgNPs, but not AgNO3, enhanced the expression levels of mitochondrial transcription factor A and peroxisome proliferator-activated receptor-gamma coactivator 1-alpha in post-MI heart and reduced the protein expression of nuclear factor-kappa B (NF-κB) assessed by western blot analysis. Furthermore, these results were confirmed with the histopathological evaluation of cardiac tissue. Nevertheless, pretreatment with either AgNO3 or AgNPs improved the aspartate aminotransferase level. Conclusion: These results suggested that AgNPs have more superior cardioprotective effect compared with AgNO3 against Iso-induced MI, at least in part through amelioration of NF-κB expression level induced by oxidative stress overproduction.

Pilot Study on the Effect of a Single Topical Application of Trichloroacetic Acid 85% on Normal Cervical Tissue.

Background: Early detection and treatment of cervical intraepithelial neoplasia (CIN) through a "see and treat" approach is a pillar of cervical cancer prevention programs in developing countries such as Indonesia. One of the major challenges faced is the limited N2O or CO2 gas supply for cryotherapy. Thus, an alternative therapeutic method such as trichloroacetic acid (TCA) topical application is needed as an alternative solution. The effectiveness of this therapy will depend on its destructive effect on eliminating the whole lesion in CIN. Objective: To estimate the extent of damage in the normal cervical tissue after a single topical application of 85% TCA solution. Design and Methods: This research was an intervention study carried out by applying ±5 ml of 85% TCA solution into the cervix of 40 patients scheduled for total hysterectomy for indications other than cervical pathology 24 h before surgery. The extent of tissue destruction was determined microscopically using histopathological specimens. The study protocol is registered at www.clinicaltrial.gov (ID NCT04911075). Results: In the final analysis, 39 subjects were included. The necrotic area was detected at the superficial layer, accompanied by the full epithelial erosion thickness. In addition, there were also fibrotic areas resembling burned tissue in the stroma. The mean depth of destruction was 1.16 ± 0.01 mm in the anterior lip and 1.01 ± 0.06 mm in the posterior lip. There was no significant depth difference between the anterior and posterior lips (p ≥0.05). Moreover, the 85% TCA topical application was tolerable, as represented by the fact that the vast majority (82.1%) of participants experienced pain with a visual analog scale score of <4. Conclusion: Single dose of TCA 85% in topical solution was able to destroy the normal cervical tissue with a deeper mean depth than the mean depth of CIN III in squamous epithelium.

Curcumin Prevents Epithelial-to Mesenchymal Transition-Mediated Ovarian Cancer Progression through NRF2/ETBR/ET-1 Axis and Preserves Mitochondria Biogenesis in Kidney after Cisplatin Administration.

Purpose: Ovarian carcinoma is one of the gynaecological malignancies that have the highest mortality rates due to its progressivity. Endothelin signalling plays a leading role in the progression of ovarian cancer through Epithelial-to-Mesenchymal Transition (EMT). Cisplatin commonly used as potent chemotherapy; however, its application hindered by its nephrotoxic effect. Curcumin, a turmeric-derived compound, has an anticancer property, as well as a renal protective effect. Moreover, curcumin augments the affinity of the antioxidant enzyme, while inhibits endothelin-1 (ET-1) signalling. The effects of curcumin on ovarian cancer progression and cisplatin-induced kidney injury remain unknown. Methods: Curcumin was used as a supplementary therapy together with cisplatin in Human Ovarian Cancer Cell line (SKOV3) and also in rodent-induced ovarian cancer. The kidney phenotype in the ovarian cancer rat model after cisplatin ± curcumin administration will also be analyzed Results: Co-treatment of cisplatin with curcumin enhanced the expression of a gene involved in apoptosis in association with NRF2 enhancement, thus activated ETBR-mediated ET-1 clearance in SKOV3 cell and ovarian cancer model in rat. Moreover, curcumin treatment improved mitochondria biogenesis markers such as PGC-1α and TFAM and prevented the elevated of ET-1-mediated renal fibrosis and apoptosis in kidney isolated from cisplatin-treated ovarian cancer rat. Conclusion: Curcumin could be potentially added as an anticancer adjuvant with protective effects in the kidney; thus, improves the efficacy and safety of cisplatin treatment in the clinical setting.

Effects of Moringa oleifera in Two Independents Formulation and as Neuroprotective Agent Against Scopolamine-Induced Memory Impairment in Mice.

Background: The cognitive deficit has frequently been found in the elderly population. Several studies have shown that every single part of Moringa oleifera, including leaves, roots, and seeds, has abundant micronutrients, such as flavonoids, which improve the neurobehavioral capacity. However, herb parts that display optimal neuropharmacological properties remain unknown. Objective: We investigate whether M. oleifera seed oil (MOO) or aqueous M. oleifera leaves extracts (MOEs) may ameliorate memory impairment in mice induced with scopolamine (Sco). Additionally, the phytochemical analyses of those two independent formulations were analyzed. Methods: In this study, 2 ml/kg body weight (BW) of MOO and 500 mg/kg BW of MOE were orally administered to the mice for 28 days, followed by intraperitoneal injection of Sco (1 mg/kg) at the day 22-28 to induce cognitive impairment in those mice. Results: The Sco group showed memory retention impairment represented by the Y-maze and novel object recognition tests, significant enhancement of acetylcholine esterase (AChE) activity in hippocampus tissue (p < 0.0001), and increased the level of total antioxidant capacity (TAOC) in serum. Interestingly, the Sco-induced memory defect was improved and completely blunted the AChE exacerbation in Sco+MOO-treated mice (p < 0.0001), although the TAOC level was comparable among the groups. Mechanistically, both tropomyosin receptor kinase B (TrkB), as a brain-derived neurotrophic factor-receptor, and nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-κB) protein expressions were enhanced with the hippocampus isolated from the Sco group. Nonetheless, pretreatment with MOO only, but not with MOE, ameliorated the enhanced protein expression levels of TrkB and NF-κB (p < 0.05 and p = 0.09, respectively). Conclusion: Our data reveal that MOO is preferable to MOE as a neuroprotective as evidenced by improving memory impairment. This effect, at least in part, through inhibiting the AChE and NF-κB activities and modulating the TrkB expression level.

Clinical characteristics of recurrent tuberculosis patients from a Jakarta hospital-based survey.

OBJECTIVE: To analyse factors affecting the recurrence of TB in a tertiary hospital in Jakarta, Indonesia. METHODS: This is a hospital-based survey, located in Jakarta, in the period of January 2014 - December 2018. All patients with recurrent TB were included in the study, while the samples with successful treatment in the same period were chosen by consecutive sampling. Statistical analysis of clinical characteristics of both study groups was conducted. RESULTS: The medical records of 2322 TB patients who presented to Sulianti Saroso Hospital were analyzed retrospectively. Ninety-four cases of recurrent TB that met inclusion and exclusion criteria were included in the study. It was observed that factors affecting recurrence of TB were medication compliance (p = .007, odds ratio (OR) 0.38 [CI 95% 0.19-0.76]) and appearance of lung cavity lesions in the first thorax x-ray examination (p < .001, OR 0.08 [CI 95% 0.03-0.20]). CONCLUSIONS: There was a relationship between recurrent TB and medication compliance and the appearance of lung cavity lesions in the first thorax x-ray examination.

Development, Characterization and Pharmacokinetic Profile of Chitosan-Sodium Tripolyphosphate Nanoparticles Based Drug Delivery Systems for Curcumin.

Purpose: This study aimed to provide the method of preparation, characterization of curcumin-loaded chitosan-sodium tripolyphosphate (NaTPP) nanoparticle, and evaluate its pharmacokinetic profiles. Methods: Curcumin-loaded chitosan-NaTPP nanoparticles were synthesized using ionic gelation methods. Curcumin was dissolved using surfactants and cosurfactants. Chitosan polymer was then mixed in the curcumin solution and dripped with NaTPP solution until nanoparticle formation. The mucoadhesive study was evaluated by measuring the fluorescence of curcumin within the prepared nanoparticles. The pharmacokinetic profiles of curcumin particles and nanoparticles were then assessed in rats by administering a single oral dose of 100 mg/kg BW. Blood samples were taken from nine predetermined time points, and curcumin plasma concentrations were then analyzed using UPLC-MS/MS. Results: The particle size of the curcumin nanoparticles obtained were 11.5 nm. Entrapment efficiency (EE) of curcumin nanoparticles were exceeding 99.97%, and drug loading capacity (DLC) was 11.34%. The mucoadhesive properties of the nanoparticles were superior to that of curcumin particles. Pharmacokinetic evaluation in rats revealed that curcumin nanoparticles resulted in an increase of area under the curve (AUC), maximum concentration (Cmax), earlier time to reach maximum concentration (Tmax), and lower clearance (CL). Conclusion: Curcumin-loaded chitosan-NaTPP nanoparticles is an effective formulation to improve curcumin plasma concentrations. Thus, enable its applications for the treatment of various diseases.

The Effect of Alpha Mangostin on Epithelial-Mesenchymal Transition on Human Hepatocellular Carcinoma HepG2 Cells Surviving Sorafenib via TGF-ß/Smad Pathways.

Purpose: This study was intended to find out the impact of alpha mangostin administration on the epithelial-mesenchymal transition (EMT) markers and TGF-ß/Smad pathways in hepatocellular carcinoma Hep-G2 cells surviving sorafenib. Methods: Hepatocellular carcinoma HepG2 cells were treated with sorafenib 10 µM. Cells surviving sorafenib treatment (HepG2surv) were then treated vehicle, sorafenib, alpha mangostin, or combination of sorafenib and alpha mangostin. Afterward, cells were observed for their morphology with an inverted microscope and counted for cell viability. The concentrations of transforming growth factor (TGF)-ß1 in a culture medium were examined using ELISA. The mRNA expressions of TGF-ß1, TGF-ß1-receptor, Smad3, Smad7, E-cadherin, and vimentin were evaluated using quantitative reverse transcriptase-polymerase chain reaction. The protein level of E-cadherin was also determined using western blot analysis. Results: Treatment of alpha mangostin and sorafenib caused a significant decrease in the viability of sorafenib-surviving HepG2 cells versus control (both groups with P <0.05). Our study found that alpha mangostin treatment increased the expressions of vimentin (P <0.001 versus control). In contrast, alpha mangostin treatment tends to decrease the expressions of Smad7 and E-cadherin (both with P >0.05). In line with our findings, the expressions of TGF-ß1 and Smad3 are significantly upregulated after alpha mangostin administration (both with P <0.05) versus control. Conclusion: Alpha mangostin reduced cell viability of sorafenib-surviving HepG2 cells; however, it also enhanced epithelial-mesenchymal transition markers by activating TGF-ß/Smad pathways.

Selected Indonesian Medicinal Plants for the Management of Metabolic Syndrome: Molecular Basis and Recent Studies.

Increased prevalence of metabolic syndrome (MetS) in the world influences quality of health in all respective countries, including Indonesia. Data from Indonesian Family Life Survey reported in 2019 showed that the prevalence of MetS in Indonesia currently is 21.66%, estimated with the provincial incidence ranging up to 50%; additionally, the most common components of MetS discovered in Indonesia were poor high-density lipoprotein (HDL) cholesterol and hypertension. Management treatment of MetS involves a combination of lifestyle changes and pharmacological interventions to decrease cerebrovascular disease. Various natural substances have been shown to govern any cardiovascular or metabolic disorders through different mechanisms, such as triggering anti-inflammation, lipid profile correction, sensitization of insulin reception, or blood glucose control. In Indonesia, the utilization of natural compounds is part of the nation's culture. The community widely uses them; even though in general, their effectiveness and safety have not been thoroughly assessed by rigorous clinical trials. Scientific evidence suggested that cinnamon, mangosteen, and curcumin, as well as their derived components possess a broad spectrum of pharmacological activity. In this review, an enormous potential of cinnamon, mangosteen, and curcumin, which originated and are commonly used in Indonesia, could be treated against MetS, such as diabetes, hyperlipidemia, hypertension, and obesity. The findings suggested that cinnamon, mangosteen, curcumin and their derivatives may reflect areas of promise in the management of MetS.

Alpha-Mangostin Improves Cardiac Hypertrophy and Fibrosis and Associated Biochemical Parameters in High-Fat/High-Glucose Diet and Low-Dose Streptozotocin Injection-Induced Type 2 Diabetic Rats.

PURPOSE: The aim of present study was to analyze the effect of alpha-mangostin on cardiac hypertrophy and fibrosis and biochemical parameters in high-fat/high-glucose diet and low-dose streptozotocin injection (HF/HG/STZ)-induced type 2 diabetic rats. METHODS: Diabetes was induced in male Wistar rats by giving a combination of high-fat/high-glucose (HF/HG) diet for 3 weeks and followed by low-dose streptozotocin intraperitoneal injection (STZ; 35 mg/kg) at Week-3 and the HF/HG diet was continued until 8 weeks. The diabetic rats were then divided into four groups (each, n=6): untreated diabetic group (HF/HG/STZ); diabetic group treated with metformin 200 mg/kg/day (HF/HG/STZ+Metformin); diabetic group treated with alpha-mangostin 100 mg/kg/day (HF/HG/STZ+AM100); and diabetic group treated with alpha-mangostin 200 mg/kg/day (HF/HG/STZ+AM200) and all were given by oral gavage for 8 weeks. We also included a control group (C) treated with AM200 (C+AM200). The role of alpha-mangostin was assessed through its effect on blood glucose levels, HOMA-IR, blood pressure, body weight, pro-inflammatory cytokines in cardiac tissue, serum aminotransferases (ALT and AST), lipid profiles (cholesterol and triglyceride), blood urea nitrogen (BUN), uric acid, cardiac hypertrophy and fibrosis. RESULTS: Diabetic rats treated with alpha-mangostin in both doses for 8 weeks showed decrease in blood glucose levels, HOMA-IR, and blood pressure. Alpha-mangostin treatment also prevented HF/HG/STZ-induced changes in the activities of ALT, AST, BUN, uric acid, lipid profiles, and pro-inflammatory cytokines, which were comparable with the standard drug metformin, while alpha-mangostin did not show any significant effects on control rats (p>0.05). The cardiac hypertrophy and fibrosis were also attenuated in diabetic rats treated with alpha-mangostin in both doses. CONCLUSION: These data suggest that administration of alpha-mangostin can effectively attenuate diabetes-induced alteration in cardiac hypertrophy and fibrosis as well as biochemical parameters in HF/HG/STZ rats.

Curcumin Nanoparticle Enhances the Anticancer Effect of Cisplatin by Inhibiting PI3K/AKT and JAK/STAT3 Pathway in Rat Ovarian Carcinoma Induced by DMBA.

Cisplatin has been used for decades for the treatment of ovarian cancer. However, despite its potent anticancer effect, cisplatin's efficacy as a single agent was inadequate in patients with advanced stage. Curcumin has been shown to sensitize cisplatin activity in several cancer models. However, the low bioavailability of curcumin has limited its anticancer potential. Hence, nano-formulation of curcumin was developed to increase its therapeutic efficacy in ovarian cancer. The objective of this study was to investigate the mechanism of curcumin nanoparticles given in combination with cisplatin in rat ovarian carcinoma induced by dimethylbenz(a)anthracene (DMBA). The administration of cisplatin and nanocurcumin resulted in a significant reduction in ovarian tumor volume and weight. Furthermore, there were reduction in expressions of Ki67, TGF-ß, PI3K, and Akt phosphorylation. Co-treatment of cisplatin and nanocurcumin also reduced JAK expression, STAT3 phosphorylation, and reduced IL-6 concentrations. Altogether, nanocurcumin, given as a co-treatment with cisplatin has therapeutic potential in ovarian cancer models by inhibiting proliferation through downregulation of PI3K/Akt and JAK/STAT3 signaling pathways.