Curcuma xanthorrhiza Roxb, Phyllanthus niruri L., and Morinda citrifolia L. are Indonesian medicinal herbs used empirically as traditional therapeutics for maintaining health. The cocktail extract of these three plants (CECPM) had been developed and demonstrated immunostimulant activity in rats. This study aimed to evaluate the acute and subchronic toxicity of CECPM in vivo. The acute toxicity assay was conducted by orally administering a range dose of CECPM (313, 625, 1250, 2500, or 5000mg/kg body weight (bw) on female mice once and then evaluating the toxic symptom every day for 14days later. The chronic toxicity test was carried out by giving various doses of CECPM (600, 800, and 1000mg/kg·bw) to female and male rats orally continuously for 90 consecutive days. The signs of toxicities were evaluated at the 90- and 28 days postadministration. The acute oral toxicity assays showed that there was no toxic syndrome and mortality found during the period of the experiment. The lethal dose level (LD₅₀) of CECPM was more than 5000g/kg, which was categorized as practically non-toxic. Meanwhile, in the sub-chronic toxicity study, some parameters tested at 90 days postadministration and after 28 days of withdrawal, such as the body weight, relative organ weight, food intake, hematological and biochemical blood parameters, and also histopathological examination of five primary tissues (heart, liver, kidney, spleen, and lung) revealed no abnormalities. There was no-observed adverse effect level (NOAEL) for the present study of CECPM 1000mg/kg·bw of the rat. Therefore, it is concluded that the orally administered CECPM was relatively nontoxic during acute and subchronic toxicology studies.

Background/Objectives: Although malaria is one of the oldest known human diseases, it continues to be a major global health challenge. According to UNICEF, the global malaria mortality rate exceeded 600,000 annually in 2022, which includes more than 1000 children dying each day. This study aimed to investigate the comprehensive chemical profile and biological activities, particularly the antimalarial activity, of Lycium shawii (Awsaj), a shrub traditionally used in the Arabian Peninsula, Middle East, India, and Africa to treat a myriad of ailments. Methods: Crude extracts of L. shawii were prepared using water, ethanol, methanol, and acetone. Nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) were utilized to perform untargeted metabolomics to maximize metabolite detection and tentatively identify bioactive phytochemicals. The total phenolic content (TPC) was measured for each extract, and bioassays were conducted to evaluate their antimalarial, antibacterial, and anti-inflammatory activities, particularly those of the water extract, which is the traditional method of consumption in Arabian folk medicine. Results: A total of 148 metabolites were detected, 45 of which were classified as phytochemicals. The bioassays revealed that the water extract that is traditionally used showed promising antimalarial potential by significantly inhibiting β-hematin formation in vitro at 1 mg/mL (with an absorbance of 0.140 ± 0.027). This is likely due to the rich presence of quinoline in the aqueous extract among several other bioactive phytochemicals, such as phenylpropanoids, alkaloids, flavonoids, and benzenoids. However, their anti-inflammatory and antibacterial activities were found to be weak, with only a minor inhibition of nitric oxide (NO) production in LPS-induced RAW 264.7 cells at a concentration of 500 µg/mL and weak antibacterial effects against pathogens like P. aeruginosa, MRSA, A. baumannii, and K. pneumoniae with an MIC of 500 μg/mL. The results also revealed that the methanolic extract had the highest TPC at 26.265 ± 0.005 mg GAE/g. Conclusions: The findings support the traditional medicinal use of L. shawii and highlight its potential as a source of novel therapeutic compounds, particularly for treating malaria. This study encourages further research to isolate and develop effective plant-based anti-malarial agents.

The wound healing process goes through a complex mechanism and takes a long time. Based on empirical experience, binahong leaves (Anredera cordifolia (Ten.) Steenis) heal fresh wounds. This study aims to determine the potential of binahong extract as an active ingredient for wound healing through in silico and in vitro testing. Extraction of the leaves using the ultrasonication method with several different solvents: ethyl acetate–ethanol and aqueous ethanol with a definite ratio. Based on UHPLC-HRMS analysis, the 96% ethanol extract identified 187 compounds, the 70% ethanol extract 153 compounds, the 50% ethanol extract 105 compounds, and the ethyl acetate extract 110 compounds. In silico study showed that the trans-3-indole acrylic acid compound with MMP1 produces a binding energy of -8.0 kcal/mol, while the MMP1 native ligand produces -9.5 kcal/mol. The gluconic acid compound with MMP12 produces a binding energy of -4.3 kcal/mol, while for the native ligand, MMP12 produces -3.4 kcal/mol. Both compounds were identified in Anredera cordifolia (Ten.) Steenis extract with a 70% ethanol solvent. An in vitro assay was conducted using a fibroblast cell proliferation assay over 24, 48, and 72 hours using the MTT method. Extract with 70% ethanol in the 24-hour incubation period significantly increased cell proliferation, but in the 48- and 72-hour incubation periods, it tended to be stable. 70% ethanol of Anredera cordifolia (Ten.) Steenis at 8 μg/mL–200 μg/mL concentrations can significantly increase cell proliferation compared to extracts with other solvents. These results indicate that the 70% ethanol extract of Anredera cordifolia (Ten.) Steenis has the best activity to accelerate the proliferation process, which can be the initial step to repair the wound. This study revealed that 70% ethanol of Anredera cordifolia (Ten.) Steenis is potent as a wound-healing agent.

Mitragynine is a natural compound found in the leaves of the Mitragyna speciosa tree, commonly known as kratom, which is primarily sourced from Southeast Asia. This review article highlights the methodologies of extraction techniques for isolating mitragynine, purification, characterization, and biosynthesis, including the complete synthesis of mitragynine and its derivatives, and briefly summarizes their biological activities and toxicology of mitragynine. The study was conducted by searching several scientific databases. There were extraction methods for mitragynine, including organic solvent extraction (hexane, chloroform, and methanol), green solvent extraction (distilled water), ultrasound-assisted extraction, and accelerated solvent extraction. The purification process of mitragynine using column chromatography with various eluen, including n-hexane, ethyl acetate, and petroleum ether. The natural mitragynine is mainly generated from the shikimate pathway and monoterpenoid secoiridoid pathway. Furthermore, there were several methods for the complete synthesis of mitragynine and the alteration of its structure. Mitragynine and its derivatives possess various pharmacological properties, including anticancer, Analgesic effects, gastrointestinal effects, antidepressant effects, Impact on cognitive function, antioxidant, and antidiabetic. The higher doses of mitragynine (100 mg/kg) in rats led to changes in hematology and the histopathological examination of the liver and brain indicates signs of toxicity.

This study aimed to evaluate the anti-inflammatory activity of the combination of Ardisia humilis Vahl. and Curcuma xanthorrhiza Roxb. (AC) extract in monosodium iodoacetate (MIA)-induced osteoarthritis (OA) rat model. AC was administered orally to OA rats (240, 480, and 960 mg/kg bw) for three weeks. The control and model groups comprised OA rats treated with diclofenac sodium and carrier, respectively. AC-treated rats exhibited a significant reduction in oedema volume compared to those of the model group (p < 0.05). Notably, AC, at 960 mg/kg bw, significantly decreased inflammatory cytokines TNF-α and IL-1β, along with matrix metalloproteinase-9 (MMP-9) levels compared to those of the model group (p < 0.05). AC's attenuation of OA progression was also observed through haematoxylin and eosin (H&E) and Safranin O-fast green analysis. A phytochemical study showed AC contained phenolic, flavonoid, curcumin, demethoxycurcumin, and bisdemethoxycurcumin compounds. This study concludes that AC alleviated OA progression through anti-inflammatory effects and depressed MMP-9 levels.

Atherosclerosis is one of the causes of cardiovascular disease (CVD). The high level of cholesterol which is controlled by 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase plays an essential role in the pathogenesis of atherosclerosis. By inhibiting the activity of HMG-CoA reductase, the biosynthesis of cholesterol may be limited and therefore contribute to the reduction of blood cholesterol. This research aims to identify the hit compounds of HMG-CoA reductase inhibitors from the natural compounds database of West Bali National Park from the Internal PRBBOT BRIN database (Indonesia's natural compounds data base). We conducted a virtual screening workflow using a quantitative structure-activity relationship (QSAR) strategy based on artificial intelligence approach to allow faster screening of HMG-CoA reductase inhibitor from 2608 compounds. Eight classifications and five regressions in machine learning algorithms were applied to build a virtual screening workflow using the 1173 compounds dataset from the ChEMBL database. The classification QSAR model used the Random Forest and Fuzzy Rule algorithm with a tied score of accuracy were 0.972 and the regression QSAR model used the Tree Ensemble algorithm with the R2 pred = 0.88. Virtual screening results identified three hit compounds as HMG-CoA reductase inhibitors from Calophyllum inophyllum L., including Inocalophyllin B, Brasiliensic acid, and Inophylloidic acid. These results indicated the benefit of the machine learning approaches for potential screening compounds as an inhibitor for the HMG-CoA reductase enzyme, and it may be useful to screen various drug candidates for other target diseases.