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1.
Arch Physiol Biochem ; : 1-11, 2023 Oct 25.
Article in English | MEDLINE | ID: mdl-37878369

ABSTRACT

Hyperglycaemia is one condition related to inflammation leading to insulin signalling impairment. This study was conducted to investigate the insulin sensitivity improvement of Sambiloto (Andrographis paniculata (Burm. f.)) Nees extract in insulin resistance-induced HepG2 (IR-HepG2) cells by stimulating insulin sensitivities and inhibiting inflammatory response. Sambiloto extract at 2 µg/mL revealed glucose uptake stimulation and up-regulating GLUT-2 and IRS-1 gene expression, and inhibited pro-inflammatory cytokine IL-6 gene expression in IR-HepG2 cells. Phytochemical analysis showed that the total phenolic level and andrografolide content of Sambiloto extract were 2.91 ± 0.04% and 1.95%, respectively. This result indicated that Sambiloto extract ameliorated insulin resistance in high glucose-induced IR-HepG2 cells via modulating the IRS-1/GLUT-2 pathway due to IL-6 inhibition. These findings suggested that Sambiloto extract had potency as an anti-inflammatory and insulin-resistance improvement in IR-HepG2 cells.

2.
J Adv Vet Anim Res ; 10(1): 126-131, 2023 Mar.
Article in English | MEDLINE | ID: mdl-37155542

ABSTRACT

Objective: The percentage of infertility cases in this world is about 50%. Seahorses (Hippocampus spp.) are widely used in traditional medicine. Several studies suggest that seahorses have ethnopharmacological characteristics, such as fertility, antioxidants, and antifatigue. The purpose of this study was to determine whether seahorse extract (SE) (Hippocampus comes L.) has an effect on fertility and serum biochemistry in rats induced by depo medroxyprogesterone acetate (DMPA). Materials and Methods: All animals were induced with 1.25 mg/kg BW of DMPA. Animals were grouped into five groups: namely aquadest, 1% CMC, and SE doses of 150, 225, and 300 mg/kg BW. The rats were gavage every morning from week 7 until 18. At the end of our study, semen from the vas deferens and blood from the heart were analyzed. We analyzed with a one-way analysis of variance and Bonferroni's post hoc tests (α 95%). Results: The concentration of spermatozoa had a significant difference in dose of 150 mg/kg BW compared to other groups (p = 0.04). In contrast, the motility (p = 0.012) and viability of spermatozoa (p = 0.007) were highly significant differences (p < 0.05 and p < 0.01) at 300 mg/kg BW. Testosterone levels were not significantly (p = 0.162; p > 0.05), but tended to increase at 300 mg/kg BW (11.01%). Nevertheless, serum biochemistry was insignificant (p > 0.05) in all groups. Conclusion: SE (Hippocampus comes L.) ameliorates fertility and serum biochemistry in rats induced by DMPA.

3.
Biomed Pharmacother ; 155: 113734, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36152408

ABSTRACT

Oxidative stress and chronic inflammation are closely linked to various diseases. However, previous studies have demonstrated that plant extracts could prevent and alleviate these adverse outcomes. Piper betle Linn. (Piper betle L.) is a cosmopolitan plant that belongs to the Piperaceae family, whose leaves are edible and possess several health benefits. This study sought to characterize the anti-inflammatory and antioxidant effects of a methanol extract of Piper betle L. leaves and stems (MPBLLS). MPBLLS was found to have a dose-dependent radical scavenging effect, as demonstrated by the 2,2-diphenyl-1-picrylhydrazyl assay. Additionally, MPBLLS inhibited the lipopolysaccharide (LPS)-stimulated production of nitric oxide and prostaglandin E2 by reducing the expression of inducible nitric oxide synthase and cyclooxygenase-2 in RAW 264.7 macrophages without affecting cell viability. Furthermore, our findings suggested that the inhibitory effects of MPBLLS on pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1ß, and interleukin-6 were due to the inhibition of the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways in LPS-treated RAW 264.7 macrophages. MPBLLS and hydroxychavicol, a major constituent of MPBLLS, suppressed LPS-induced translocation of NF-κB p65 from cytoplasm to nucleus. Interestingly, MPBLLS increased nuclear factor erythroid 2-related factor 2 (Nrf2) protein levels and transcription levels of Nrf2 target genes in a dose-dependent manner. Collectively, our findings suggest that MPBLLS could serve as a basis for the development of novel orally-administered therapies due to its inhibitory effects on oxidative and inflammatory stress. DATA AVAILABILITY: The data presented in this study are available on request from the corresponding author.


Subject(s)
NF-kappa B , Piper betle , Mice , Animals , NF-kappa B/metabolism , Nitric Oxide Synthase Type II/metabolism , Antioxidants/pharmacology , Antioxidants/metabolism , Lipopolysaccharides/pharmacology , Lipopolysaccharides/metabolism , NF-E2-Related Factor 2/metabolism , Interleukin-1beta/metabolism , Methanol/pharmacology , Cyclooxygenase 2/metabolism , Nitric Oxide/metabolism , Tumor Necrosis Factor-alpha/metabolism , RAW 264.7 Cells , Interleukin-6/metabolism , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/metabolism , Macrophages , Plant Extracts/pharmacology , Plant Extracts/metabolism , MAP Kinase Signaling System , Cytokines/metabolism , Mitogen-Activated Protein Kinases/metabolism , Prostaglandins/metabolism
4.
J Adv Vet Anim Res ; 9(4): 610-616, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36714522

ABSTRACT

Objective: Indonesia is an archipelagic country with a mega biodiversity, among others, in the marine area. Seahorses (Hippocampus spp.) are a marine fish known to have biocompounds used in traditional medicine "Jamu," such as Hippocampus comes L. (HCL). The present study aims to analyze and compare the chemical contents of cultured seahorse (CS) and natural seahorse (NS) extracts. Materials and Methods: The CS and NS were identified morphometrically. After freeze-drying, the seahorses were ground into powder with a grinder. The seahorse powder was extracted with ethanol and a water solvent. The extract contained biocompounds, proximate, amino acids, and steroids with high-performance liquid chromatography. Results: The study found unique characteristics of HCL. The highest yield was obtained in NS using a water solvent (18.6%). The biocompounds in seahorses consist of alkaloids and triterpenoids. The highest proximate of water content (11.03%) and ash content (42.50%) was found in NS. In addition, other compounds were also detected in CS, such as fat (7.48%) and protein (47.67%). Both of HCL's different sources had all essential and nonessential amino acids in which the highest concentration were in NS, i.e., L-arginine (56,537.22 mg/kg), L-lysine (17,794.17), glycine (113,649.80 mg/kg), L-proline (47,056.15), and L-alanine (43,451.81). The analysis of the steroid compound of the extract suggested the presence of steroid glycosides. Conclusion: The highest yield of the seahorse extract with a water solvent is about 18.6% and protein content of 47.67% in CS. The crude extract has alkaloids, triterpenoids, and glycine (113,649.80 mg/kg) in NS with water, suggesting the presence of steroid glycosides.

5.
Parasitol Int ; 85: 102432, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34363974

ABSTRACT

Microorganisms in nature are highly diverse biological resources, which can be explored for drug discovery. Some countries including Brazil, Columbia, Indonesia, China, and Mexico, which are blessed with geographical uniqueness with diverse climates and display remarkable megabiodiversity, potentially provide microorganismal resources for such exploitation. In this review, as an example of drug discovery campaigns against tropical parasitic diseases utilizing microorganisms from such a megabiodiversity country, we summarize our past and on-going activities toward discovery of new antimalarials. The program was held in a bilateral collaboration between multiple Indonesian and Japanese research groups. In order to develop a new platform of drug discovery utilizing Indonesian bioresources under an international collaborative scheme, we aimed at: 1) establishment of an Indonesian microbial depository, 2) development of robust enzyme-based and cell-based screening systems, and 3) technology transfer necessary for screening, purification, and identification of antimalarial compounds from microbial culture broths. We collected, characterized, and deposited Indonesian microbes. We morphologically and genetically characterized fungi and actinomycetes strains isolated from 5 different locations representing 3 Indonesian geographical areas, and validated genetic diversity of microbes. Enzyme-based screening was developed against two validated mitochondrial enzymes from Plasmodium falciparum, dihydroorotate dehydrogenase and malate:quinone oxidoreductase, while cell-based proliferation assay was developed using the erythrocytic stage parasite of 3D7 strain. More than 17 thousands microbial culture extracts were subjected to the enzyme- and cell-based screening. Representative anti-malarial compounds discovered in this campaign are discussed, including a few isolated compounds that have been identified for the first time as anti-malarial compounds. Our antimalarial discovery campaign validated the Indonesian microbial library as a powerful resource for drug discovery. We also discuss critical needs for selection criteria for hits at each stage of screening and hit deconvolution such as preliminary extraction test for the initial profiling of the active compounds and dereplication techniques to minimize repetitive discovery of known compounds.


Subject(s)
Antimalarials/isolation & purification , Antimalarials/pharmacology , Drug Discovery , Plasmodium falciparum/drug effects , Indonesia
7.
PLoS One ; 15(11): e0240020, 2020.
Article in English | MEDLINE | ID: mdl-33211707

ABSTRACT

Breast cancer stem cells (BCSCs) express high levels of the anti-apoptotic protein, survivin. This study aimed to discover a natural active compound with anti-cancer properties that targeted survivin in human breast cancer stem cells. From the seven examined compounds, andrographolide was selected as a lead compound through in silico molecular docking with survivin, caspase-9, and caspase-3. We found that the affinity between andrographolide and survivin is higher than that with caspase-9 and caspase-3. Human CD24-/CD44+ BCSCs were treated with andrographolide in vitro for 24 hours. The cytotoxic effect of andrographolide on BCSCs was compared to that on human mesenchymal stem cells (MSCs). The expression of survivin, caspase-9, and caspase-3 mRNA was analyzed using qRT-PCR, while Thr34-phosphorylated survivin and total survivin levels were determined using ELISA and Immunoblotting assay. Annexin-V/PI flow cytometry assays were performed to evaluate the apoptotic activity of andrographolide. Our results demonstrate that the CC50 of andrographolide in BCSCs was 0.32mM, whereas there was no cytotoxic effect in MSCs. Moreover, andrographolide decreased survivin and Thr34-phosphorylated survivin, thus inhibiting survivin activation and increasing survivin mRNA in BCSCs. The apoptotic activity of andrographolide was revealed by the increase of caspase-3 mRNA and protein, as well as the increase in both the early and late phases of apoptosis. In conclusion, andrographolide can be considered an anti-cancer compound that targets BCSCs due to its molecular interactions with survivin, caspase-9, and caspase-3, which induce apoptosis. We suggest that the binding of andrographolide to survivin is a critical aspect of the effect of andrographolide.


Subject(s)
Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , Diterpenes/pharmacology , Neoplastic Stem Cells/drug effects , Survivin/metabolism , Apoptosis/drug effects , Caspase 3/metabolism , Caspase 9/metabolism , Cell Line, Tumor , Humans , Mesenchymal Stem Cells/drug effects , Molecular Docking Simulation
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