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Andrographis paniculata tablets (AS201-01) have previously been shown to have potent bioactivity as an antimalarial and to produce no unwanted side effects in animal models. Here, we present the phase 1 clinical trial conducted to evaluate the safety of AS201-01 tablets in healthy volunteers. The study was a randomized, double-blind controlled cross-over, a placebo-controlled design consisting of a 4-day treatment of AS201-01 tablets. A total of 30 healthy human volunteers (16 males and 14 females) were divided into two groups, and each group was given 4 tablets, twice daily for 4 days. Group 1 received AS201-01, while group 2 received placebo tablets. Volunteers were given a physical examination before the treatment. The effects of AS201-01 on random blood glucose, biochemical, and hematological as well as urine profiles were investigated. There were no changes in observed parameters as a result of AS201-01 being administered. Statistical analysis showed no significant difference (p>0.05) between the test and control group regarding hematology profile, biochemical profile, and random blood glucose. Increased appetite and better sleep, which categorized as grade 1 adverse event was reported after treatment with AS201-01 tablet The outcome supports our previous observation that the AS201-01 tablet, given twice a day for 4 days, is safe and nontoxic. [ABSTRACT FROM AUTHOR]

The use of standard antimalarial drugs, such as dihydroartemisinin-piperaquine (DHP) for the treatment of malaria during pregnancy is limited due to the risk of teratogenicity. The alternative is therefore required although few exist. Here we show a phytopharmaceutical drug derived from Andrographis paniculata (AS201-01), which is effective as herbal antimalarial both in vitro and in vivo and may be a suitable alternative when used in complementary treatment with DHP. Plasmodium berghei infected pregnant BALB/c mice were divided into four groups: G1 (negative control), G2 (AS201-01), G3 (DHP), and G4 (combination of DHP and AS201-01). Pheripheral blood was collected during therapy for counting parasitemia. Placental samples were analyzed for the expression of IFN-γ, TNF- α, IL-10, placental parasite counts and foetal morphology. Groups G4 and G3 both showed a 100% inhibition of peripheral parasitemia. However, the treatment in G4 was found to be less effective than that in G2 and G3 in preventing placental parasitemia. The G4 treatment was able to reduce the expression of IFN-γ and IL-10, whereas TNF-α was not significantly different from the control group. Foetal morphologic abnormalities were observed in all groups except G2; G4 showed lower percentage of abnormalities compared to G3 and G1. A combination of A. paniculata tablet (AS201-01) with DHP has the potential to reduce the toxicity of DHP in malaria treatment. [ABSTRACT FROM AUTHOR]

Objectives: The rapid spread of antimalarial drug resistance is becoming a problem in the treatment of malaria. The fact was indicated the importance of finding new antimalarial drugs. The genus Garcinia is well known to be a rich source of bioactive prenylated xanthones and triterpenes reported for their antimalarial activity. Garcinia parvifolia is one of the Garcinia genera that can be explored for the search of new antimalarial drugs. This study was aimed to determine the antimalarial activities of G. parvifolia extracts and fractions. Methods: Garcinia parvifolia Miq. stem was collected from Balikpapan Botanical Garden in East Kalimantan, Indonesia, was extracted gradually with n-hexane, dichloromethane, and methanol by ultrasonic assisted method. The most active extract was further separated using the open column chromatography method. All extracts and fractions were tested against Plasmodium falciparum 3D7 using lactate dehydrogenase (LDH) assay and followed by IC50 determination. Results: The results showed that all extracts inhibit P. falciparum growth by LDH assay. The highest inhibition was showed by dichloromethane stem extract (BP12-S-D) with the IC50 value of 6.61 ± 0.09 μg/mL. Further fractionation of BP12-S-D has obtained 10 fractions. All of them were identified by TLC, and a brownish-yellow spot (fraction-1) appears after spraying with 10% H2SO4. Fraction-1 (F1) performed the highest parasite growth inhibition with the IC50 value of 6.00 ± 0.03 μg/mL compared with other fractions. This fraction was classified as having a promising activity of antimalarial. The fraction-1 was identified using HPLC, and two major peaks were observed (A and B). The UV–Vis spectra showed the absorption at wavelengths 250 and 278 (A), 243, 281, and 317 nm (B). Based on the profile of TLC, HPLC, and UV–Vis spectra of F1, it was expected that the active compounds are flavonoid (A) and xanthone (B). Conclusions: The fraction-1 of dichloromethane extract of G. parvifolia Miq. stem has the highest antimalarial activity. It might be a potential candidate for the new antimalarial drug. [ABSTRACT FROM AUTHOR]

Phyllanthus niruri has been known as an immunomodulator and also reported to possess an antiviral activity against several RNA viruses, such as hepatitis B virus and hepatitis C virus by inhibiting viral entry and replication. Since the current situation of Coronavirus Disease 2019 (COVID-19) which infected among the world and caused severe disease and high morbidity, it urgently needed to find new agents against COVID-19. Therefore, in silico screening against COVID-19 receptors is carried out as an initial stage of drug discovery by evaluating the activity of phyllanthin and hypophyllanthin, an isolated from Phyllanthus niruri, in inhibiting spike glycoprotein (6LZG) and main protease (5R7Y) which play as target receptors of COVID-19. Molegro Virtual Docker 6.0 used to determine the best binding energy through the rerank score which shows the total energy bonds calculation. Phyllanthin and hypophyllanthin demonstrated to possess greater binding affinity toward the COVID-19 inhibition sites than their native ligand. The rerank score of phyllanthin and hypophyllanthin are lower than the native ligands 6LZG and 5R7Y. This result indicated that phyllanthin and hypophyllanthin have a stronger interaction than the native ligands both in spike glycoprotein (entry inhibitor) and main protease (translation and replication inhibitor). In conclusion, phyllanthin and hypophyllanthin are predicted to have strong activity against COVID-19 through inhibiting spike glycoprotein and main protease under in silico study. Further research is needed to support the development of P. niruri as inhibitor agents of COVID-19 through bioassay studies. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus (HIV) infection is considered as a major immunosuppressive disease linked to malignancies and other opportunistic infections. Recently, the high prevalence of HIV drug-resistant strains required a high demand for novel antiviral drug development, especially in herbal medicine approaches. The objective of this study was to evaluate the possibility of Ficus fistulosa leaves can inhibit HIV replication in ethanol extract form as well as its fractions using chloroform, ethyl acetate, and butanol solvents. F. fistulosa leaves were extracted using ethanol as a solvent and further gradually fractionated in chloroform, ethyl acetate, and butanol solvents. The targeted persistently infected virus (MT4/HIV) cell lines were cocultured with ethanol extract and fractions at different time points. The syncytium formation and cytotoxicity assays were performed to evaluate the potential antiviral activity of F. fistulosa leaves. One of the four tested extract/fractions showed antiviral activity against HIV. The ethanol extract showed weak inhibition with a high level of toxicity (IC50 = 8.96 μg/mL, CC50 ≥50 μg/mL, and SI = 5.58). Meanwhile, chloroform fraction effectively inhibited the MT4/HIV cell proliferation while keeping the toxicity to a minimal level (IC50 = 3.27 μg/mL, CC50 = 29.30 μg/mL, and SI = 8.96). In contrast of ethyl acetate fraction and butanol fraction showed no anti HIV activity with a high level of toxicity (CC50 ≥50 μg/mL) and low SI value (>2.17 μg/mL and >0.97 μg/mL). Chloroform fraction of F. fistulosa leaves showed effectively as anti-viral activity against MT4/HIV cells. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a degenerative brain disease characterized by confusion, behavior changes, decline in memory and cognitive skills. One of the strategies in the treatment of AD is to use acetylcholinesterase (AChE) inhibitors. The current study aims to determine the AChE inhibitory activities of the extract and fractions of the root of Rauvolfia serpentina. Extraction was carried out by maceration method using ethanol, followed by liquid–liquid partition using n-hexane, ethyl acetate and n-butanol. Further fractionation was conducted by using vacuum liquid chromatography (VLC). The AChE inhibitory assays were performed by using Ellmann's method. Phytochemical screening was carried out by TLC method. The ethanolic extract of R. serpentina showed inhibition against AChE enzyme with an IC50 value of 7.46 μg/mL. The extract and fractions showed higher inhibition against butyrylcholinesterase (BChE) compared to AChE. Amongst three fractions obtained, the n-butanol fraction showed the strongest inhibition with an IC50 value of 5.99 μg/mL against AChE. VLC fractionation of the n-butanol fraction yielded 13 subfractions (VLC 1–VLC 13). Four out of 13 subfractions gave more than 80% inhibition against AChE, namely subfractions 4–7, with IC50 values ranging from 4.87 to 47.22 μg/mL. The phytochemical screening of these subfractions suggested the presence of alkaloids. The ethanolic extract, as well as fractions of R. serpentina root, are potential for AChE inhibitor. The alkaloid compound may be responsible for this activity. [ABSTRACT FROM AUTHOR]

The antimalarial drug resistance is an obstacle in the effort to overcome malaria. The new alternative antimalarial drug became in great attention of urgent need. Current antimalarial drugs were derived from plants. Therefore, the plant is considering a potential source of new drugs. Cratoxylum sumatranum belongs to the Hypericaceae family contain xanthones and phenolic compounds, which was reported for their antimalarial activities. This study aims to determine the antimalarial activities of C. sumatranum extracts and fractions. Cratoxylum sumatranum stem bark (BP14-SB) collected from Balikpapan Botanical Garden in East Kalimantan, Indonesia, was extracted gradually with n-hexane, dichloromethane, and methanol by ultrasonic-assisted extraction method. All extracts were tested against Plasmodium falciparum 3D7 by lactate dehydrogenase (LDH) assay and followed by IC50 determination. The most active extract was further separated and tested for their antimalarial activities. The results showed that dichloromethane stem bark extract (BP14-SB-D) had the strongest inhibition of parasite growth with the IC50 value of 0.44 ± 0.05 μg/mL and moderately toxic with the CC50 value of 29.09 ± 0.05 μg/mL. Further fractionation of BP14-SB-D by open column chromatography using silica gel and gradient hexane–ethyl acetate obtained 12 fractions. LDH assay for these 12 fractions of BP14-SB-D showed that Fraction-6 (IC50 value of 0.19 ± 0.03 μg/mL) was performed the strongest inhibition of parasite growth, compared to other fractions. TLC identification showed that BP14-SB-D contains xanthone. The dichloromethane extract of C. sumatranum stem bark (BP14-SB-D) and Fraction-6 from this extract exhibited antimalarial activity and the potential to be developed an antimalarial substance. [ABSTRACT FROM AUTHOR]

Background: Medicinal plants are known to perform many pharmacological actions due to their chemical metabolites, which include antiviral effects. Previously, the extract of Ruta angustifolia was shown to have potential anti-hepatitis C virus (HCV) activity without any cytotoxicity, with a 50% inhibitory concentration of 3.0 μg/mL and a 50% cytotoxicity concentration of >100 μg/mL. Furthermore, the combination of medicinal plants and current anti-HCV agents, such as a direct-acting antiviral agent, was shown to potentiate their overall effectiveness. In the course of this study, the ethanolic extract of R. angustifolia was evaluated for its anti-HCV effects; specifically, the mechanism of action on HCV NS3 and NS5A protease was investigated. Methods: Analysis of the use of this extract in conjunction with current NS3 inhibitor drugs, simeprevir (SMV) and telaprevir (TVR), was performed. Anti-HCV activity was performed by in vitro culture of hepatocyte cells. The cells were infected and treated with various concentrations of the sample. HCV inhibition was calculated and CompuSyn software analysis was used to determine the synergistic effect of the combination. Results: Results demonstrated that R. angustifolia extract inhibited the post-entry step and decreased the protein levels of HCV NS3 and NS5A. The combination of extract and SMV and TVR mediated a synergistic effect. Conclusions: These findings suggest that combining R. angustifolia extract with current anti-HCV drugs should be considered when developing alternative and complementary anti-HCV medicines. [ABSTRACT FROM AUTHOR]