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Aplastic anemia, life-threatened disease, is a hematologic disorder characterised by bone marrow hypoplasia. Multiple modalities such as bone marrow transplantation and immunosuppression treatment have been proposed to ameliorate this entity, however it remains ineffective. Sambucus, a group of herb plants, possesses a broad spectrum of medicinal properties such as antioxidant, insulin-like activity, anticancer and antiviral. However, the study about its activity toward aplastic anemia incidence is based on limited data. Thus, the research aim of this study was to evaluate the immunomodulatory activities of Sambucus javanica in chloramphenicol-induced anemia aplastic mouse model. In this present study, BALB/c mice were administrated with chloramphenicol (CMP) to induce aplastic anemia then followed by S. javanica extracts treatment. Additionally, cellular and molecular aspects were evaluated by flow cytometry and Hematoxylin-Eosin staining. Further analysis showed that S. javanica extracts could promote the population number of regulatory T-cells and naive cytotoxic T-cells. Moreover, those extract also reduced the inflammation and necrotic incidence in CMP-induced mouse aplastic anemia model. Together, these results suggest that S. javanica has therapeutically effect to aplastic anemia by altering the immune system as an immunomodulatory agent.

Dengue caused by the dengue virus (DENV) is a severe health problem in tropical regions such as Southeast Asia, especially Indonesia. Indonesian have used rhizome as traditional medicine for 1300 years. This study investigated the compounds from Kaempferia galanga, Curcuma longa, Zingiber officinale, Curcuma aeruginosa, Curcuma zanthorrhiza, Alpinia galanga, and Allium sativum as antivirals agents, explicitly targeting the DENV envelope protein to inhibit viral fusion. This study involved 121 bioactive compounds and DENV2's prefusion envelope protein. The virtual screening and molecular docking were done through occupied the Lipinski rule of five checker (http://www.scfbio-iitd.res.in/software/drugdesign/lipinski.jsp) and AutoDock Vina (https://pyrx.sourceforge.io/) respectively. The top nine compounds with the strongest binding affinity were galangin, kampferide, demetoxy curcumin, bisdemethoxycurcumin, β-selinene, 6-(hydroxymethyl)-1,4,4-trimethylbicyclo[3.1.0]hexan-2-ol, piperine, estra-1,3, 5(10)-trien-17β-ol, and curcumin. These compounds' affinity values were significantly lower, around 45-62%, than chloroquine. Most of them interact with the kl hairpin and hydrophobic pocket formed by residues Val130, Leu135, Phe193, Leu198, and Phe279of critical domains that can interfere with the conformational change and rearrangement of protein dimer in the post-fusion stage. This study suggested that the galangin, demethoxycurcumin, and bisdemethoxycurcumin are considered the most potential compounds to be developed as anti-prefusion E DENV2 low-affinity and intense interaction with those. Keywords: DENV2, envelope protein, in silico, viral fusion, viral infection

Purpose: Accumulating evidence shows the genus of Sambucus exerts a broad spectrum ofmedicinal potencies such as anticancer, antiviral, antibacterial, and antidiabetes. Based on theprevious studies, we hypothesized that bioactive compounds of Sambucus might alter severalbiological systems, including the immune system. Therefore, this study extensively aimed toevaluate the immunomodulatory activities of Sambucus javanica extracts in 7,12-dimethylbenz[a]anthracene (DMBA)-treated BALB/c mouse.Methods: The experimental mice were orally administrated with 2.8 mg.kg-1 BW of DMBA forten times within a month. After that, the mice were treated by S. javanica berries and leavesextracts for 2 weeks. Subsequently, the inflammation rate was evaluated by using flow cytometryanalysis, whereas the necrosis incidences were observed by hematoxylin & eosin staining.Results: Based on the results, we found the expression of tumor necrosis factor alpha (TNF-α)and interferon gamma (IFN-ɣ) were increased however after treated by S. javanica berries andleaves extracts were significantly decreased. In the same way, necrosis incidence was increasedin the DMBA-treated group however it was diminished with S. javanica extracts treatment.Conclusion: Together, these results suggested that S. javanica extracts have immunomodulatoryactivities to suppress inflammation and reduce necrosis incidence in experimental mice.

Nicotine dependence can cause numerous adverse effects, especially cardiovascular, cancer, respiratory, and gastrointestinal diseases. In order to minimize the manifestation of nicotine, inhibition on the receptor's binding site is needed. Our previous in silico study shows the activity of several bioactive compounds from Camelia sinensis, Orthosipon aristatus, and Moringa oleifera might be potent as α-3 nicotinic acetylcholine receptor. Thus, in this present study, we extend the screening of inhibitor potency from Kaempferia pandurata, Camelia sinensis, Centella asiatica, Moringa oleifera, and Orthosipon aristatus bioactive compounds against the α-2 NAchR. In silico approach was performed to screen and predict the possibility of drug-likeness and medicinal plant properties of bioactive compounds. The 2D and 3D structures of ligands and protein were retrieved from PubChem and SWISS Model, respectively. The molecular docking strategy and optimization, also visualization were occupied as our previous study. The present findings show that the bioactive compounds from K. pandurata, C. sinensis, C. asiatica, M. oleifera, and O. aristatus have the possibility to be potential α-5 NAchR inhibitor.

Recently, diabetes mellitus (DM) still become the top health problem worldwide. Several reports showed the incidence and death number of this disease are increasing every year. Therefore, the strategy to overcome DM is crucially needed. Another possible way to minimize the adverse effect of DM is by understanding the immunological activities and properties, which lead us to have another option or insight to treat DM. Thus, in this present study, we aim to evaluate the production of granzyme by CD8 T cells and NK.1.1 natural killer (NK) cells after treated by the combination of Momordica charantia and Averrhoa bilimbi extract in streptozotocin (STZ) induced mice. The animal mice model was firstly induced by STZ, then followed by the Momordica charantia and Averrhoa bilimbi extract treatment. Finally, the expression number of granzyme from CD8 T cells and NK1.1 NK cells was evaluated using flow cytometry (FACS CaliburTM). According to our observation, we found that the granzyme is not produced by both CD8 T cells and NK1.1 NK cells, even after treated by the Momordica charantia and Averrhoa bilimbi extract.

Liver fibrosis is the initial step of hepatocellular carcinoma (HCC). Liver fibrosis can be triggered by metabolic perturbation, viral infection, and harmful chemical exposure. This in vivo study aims to investigate the potential of Moringa oleifera leaf powder (MOLP) from Madura Island as the future candidate for antifibrosis and hepatoprotective agent. The study was conducted to evaluate the alteration of circulating levels of liver injury marker-linked liver fibrosis development, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST). The animal model was prepared using Balb-c mice age 6-8 weeks treated by intraperitoneal injection of carbon tetrachloride (CCl4) dose 1 µL/g of BW for six weeks to induce liver fibrosis. The experimental groups were received green materials Moringa oleifera leaf powder solution with a serial dosage by peroral administration for six weeks. Interestingly, our animal model's preliminary study shows that the administration of green materials MOLP can alleviate the increase of ALT and AST. MOLP treatment can also prevent significant changes in liver weight, morphology, and even histological feature-associated liver injury and fibrosis. Hence, MOLP Madura Island may become the future green materials source for cancer herbal drug development.

Chronic inflammation is the initial stage of liver fibrosis-related hepatocellular carcinoma (HCC) development. Also, HCC is a global disease resulting from several etiological factors. HCC incidence can be triggered by alcohol abuse, non-alcoholic steatohepatitis (NASH), viral hepatitis B (HBV), viral hepatitis C (HCV), and non-alcoholic fatty liver disease (NAFLD). Liver chronic inflammation significantly correlates to TNF-α (Tumor Necrosis Factor-α) and IL-6 (interleukin 6) expression. This laboratory work aimed to investigate the effect of green material Moringa oleifera leaf powder (MOLP) on the expression of both pro-inflammatory cytokines. A semi-quantitative approach quantified the expression of TNF-α and IL-6. This research was conducted using an animal model induced by intraperitoneal injection of CCl4 solution. The results showed that green material Moringa oleifera could reduce IL-6 and TNF-α expression. Importantly, MOLP exposure can decrease the pro-inflammatory cell population in the liver parenchymal area. Hence, the application of green material Moringa oleifera might be potential as the local bioresources agent against liver inflammation-linked fibrosis. The exploration of MOLP in the future drug discovery model may significantly contribute to the prevention of hepatocellular carcinoma.

Rohman F, Putra WE. 2021. Short Communication: The bioinformatics perspective of Foeniculum vulgare fruit's bioactive compounds as natural anti-hyperglycemic against alpha-glucosidase. Biodiversitas 22: 79-84. The management in controlling the blood glucose level is crucially necessary to be promoted. Many reports showed the harmful effect of glucose toxicity, most of them are the cluster of metabolic disorder. Nowadays, natural products are getting much attention on health issues. The uses of medicinal plants for drug materials are dramatically increasing. In our previous study about local medicinal plants identification, we found that Tengger Tribe in Indonesia uses numerous type of species, including Foeniculum vulgare which was widely found and occupied as traditional medicine by Tengger Tribe in the area of Taman Nasional Bromo Tengger Semeru, East Java, Indonesia. According to their local belief, F. vulgare has been used to ameliorate several types of diseases. Thus, in this present study, we aimed to virtually evaluate the bioactive compounds of F. vulgare for anti-hyperglycemic against the alpha-glucosidase. We performed computational prediction of ligands-protein interaction by molecular docking approaches. The 2D structure of ligands and 3D structure of target protein were retrieved via the database. The natural compound's structure was then evaluated by the Lipinski rule of five to indicate whether it can be categorized as drug-like or not. Moreover, according to our simulation, F. vulgare fruit's bioactive compounds including sterol, anethole, and fenchone might have therapeutic effect to reduce the hyperglycemia incidence by inhibiting the alpha-glucosidase activity. Compared to miglitol, an alpha-glucosidase inhibitor, Sterol have the most significant binding affinity against the alpha-glucosidase. Therefore, these findings suggest that sterol, anethole, and fenchone might be potential new candidates for alpha-glucosidase inhibitors.

Dengue is a severe health problem, especially in under-developing countries like Indonesia. The government and the community have made various efforts. However, the current programs are focusing on controlling disease vector. Medical treatment so far only treats the symptoms. On the other hand, the development of antiviral compounds has been dominated by synthetic compounds which may have serious side effects. The potential of natural compounds in Asia is still largely unexplored. Dengue virus nonstructural protein 5 (NS5) is highly conserved in all serotypes. This study aims to screen several potential natural compounds to be developed as specific antiviral compounds targeting DENV NS5. This research conducted by using in silico approaches including data mining, molecular docking, and 2D-3D visualization. About 170 compounds from 88 organisms analyzed to get the top nine compounds with the highest affinity against NS5 protein. The top nine compounds are from the halichondramide, trigocherriolide, quinadoline, tryptoquivaline, and zingiberene groups. The docking results showed that these potential compounds have an affinity of about 67-100% higher than ribavirin. The visualization results show that these compounds are grouped into three different binding sites. They are RdRP, MTase, and the junction. Compounds that bind in RdRP are thought to interfere with the process of RNA viral synthesis, compounds that bind to MTase are thought to disrupt the viral RNA capping process, while compounds that bind between the two domains are thought to interfere NS5 structural integrity. The compound with the highest affinity is halishigamide A. Halishigamide A is known to have antimicrobial properties, but the action mechanism is still unknown. Compared to the control drug, the halishigamide A tends to have more dynamic movement and interaction to the target protein’s binding site due to its residues’ chemicals motive. Together, these results showed the potency of natural products as specific antiviral compounds targeting DENV NS5.

Yani A, Amin M, Rohman F, Suarsini E, Putra WE. 2020. Profiling indigenous lead-reducing bacteria from Tempe Lake, South Sulawesi, Indonesia as bioremediation agents. Biodiversitas 21: 4778-4786. The pollution of heavy metals by anthropogenic activities in freshwater, especially in lakes, reduces the quality and endangers the existence of aquatic flora and fauna. This happens in Lake Tempe, which is located, in South Sulawesi, Indonesia. The study aimed to evaluate the content of heavy metals, isolation, and identify a lead reduction of indigenous bacteria as candidates for bioremediation agents. It began by examining the level of cadmium (Cd), copper (Cu), and lead (Pb) in seven sampling sites of Tempe Lake. Furthermore, propagation and isolation, morphological observation, laboratory-scale reduction tests, and species identification of potential bacteria reduction Pb were performed by using 16s rDNA. The reduction test to Pb was measured using Atomic Absorption Spectrometry (AAS), and the research data were analyzed using One-Way ANOVA with the Duncan advanced method. The results showed that the Cd, Cu, and Pb content of the seven sampling points exceeded the water quality standard Following the Indonesian Government Regulation (IGR) and WHO standards. Pb has the highest concentration among the other heavy metals in the water sample reaching 0.40 mg/L. Four bacterial isolates could grow on Pb-enriched media (isolates A, B, C, and D). The Bacillus form was found in two different species bacteria (isolate A and D), while the cocci shape was found in two other species (isolate B and C). Those all Gram-negative bacteria were observed to be a reduction to Pb exposure within a bacterial medium. Interestingly, these indigenous bacteria could decrease Pb concentration ranging from 7.45 to 3.48 ppm for seven days. Furthermore, the sequencing data showed that the indigenous bacteria (isolate D) had a 99.90% similarity to the Comamonas testosteroni strain S-2 constructed using Neighbor-joining phylogenetic analysis. Therefore, the indigenous bacteria C. testosteroni strain S-2 from Tempe lake may be proposed as a bioremediation agent to reduce Pb the water contaminants.

Recent trends in health care demonstrate the significant use of herbs as preventive or therapeutic agents against multiple types of diseases, including respiratory disorder caused by cigarette smoking. Thus, in this present study, we explored the potential of medicinal plants’ phytochemical compounds as an inhibitor against the human α-3 nicotinic acetylcholine receptor (NAchR). The computation prediction was performed to evaluate the energy and possible interactions among the ligands and target protein. Specifically, the 2D structure of bioactive compounds was retrieved from PubChem database. On the other hand, the protein sequences of human α-3 NAchR were obtained from Uniprot and protein database. The 3D structure was then built up through SWISS-MODEL. Additionally, protein and ligand preparation was employed to optimize the molecular interaction results. The final step of this screening through molecular docking approach was performed using data visualization and analysis. In this study, we found that there are three potential compounds as an inhibitor against α-3 NAchR based on their energy-free binding, namely, Theaflavin-3-Gallate, Asiaticoside, and Theaflavin-3,3-Digallate. Therefore, work indicates that the medicinal plants’ bioactive compounds might be the potential to develop as inhibitory agents for α-3 NAchR to minimize the negative effect of nicotine.

Hematopoiesis play important roles on maintaining body homeostasis. Dexamethasone (Dex) known as synthetic glucocorticoids and widely affect many regulations i.e. immune system, inflammation, reproduction and all aspects of metabolism. Generally Dex were used as therapeutic agentsto ameliorate many kind of diseases including cancer and auto-immune diseases. The aims of this research were to investigate the effect of Dex administration toward expression of hematopoietic stem cells and blood progenitor cells. Two weeks old BALB/c mice were used and treated with 3 groups of Dex administration i.e. untreated-mice, 0.5 mg/kg BW, and 10 mg/kg BW. Mice were sacrificed on day-7 after administration of Dex. The bone marrow stromal cells were isolated, then followed by flow cytometry analysis. The result showed that, Dex administration with dose 0.5 mg/kg BW significantly increase the expression of hematopoietic stem cells, CD34 + , chemokines, SDF-1 + , erythroid progenitor cells, Gr-1 - TER-119 + , granulocytes, Gr-1 + , and B progenitor cells, B220 + .

Hematopoiesis has a pivotal role in the maintenance of body homeostasis. Ironically, several hematological disorder caused by chemicals, drugs, and other environmental factors lead to severe bone marrow failure. Current treatments like stem cell transplantation and immunosuppression remain ineffective to ameliorate this diseases. Therefore, a newtreatment to overcome this entity is necessary, one of them by promoting the usage of medicinal plants. Thus, this study aimed to evaluate the hematopoiesis potency of S. javanica berries and leaves extracts in chloramphenicol (CMP)-induced aplastic anemia mice model. In this present study, several types of blood progenitor cell such as TER-119+VLA-4+ erythrocytes lineage, Gr-1+ granulocytes, and B220+ Bcell progenitor cells were evaluated by flow cytometry analysis. Accordingly, we revealed that S. javanica berries and leaves extracts significantly promoted TER-119+VLA-4+ erythrocytes lineage and Gr-1+ granulocytes after exposed by CMP. Thus, these results suggested that S. javanica berries and leaves extracts might have hematopoiesis activity in CMP-induced aplastic anemia mice model.

The ability of tumor cells to escape immune destruction and their acquired resistance to chemotherapy are major obstacles to effective cancer therapy. Although immune checkpoint therapies such as anti-PD-1 address these issues in part, clinical responses remain limited to a subpopulation of patients. In this report, we identified IL34 produced by cancer cells as a driver of chemoresistance. In particular, we found that IL34 modulated the functions of tumor-associated macrophages to enhance local immunosuppression and to promote the survival of chemoresistant cancer cells by activating AKT signaling. Targeting IL34 in chemoresistant tumors resulted in a remarkable inhibition of tumor growth when accompanied with chemotherapy. Our results define a pathogenic role for IL34 in mediating immunosuppression and chemoresistance and identify it as a tractable target for anticancer therapy. Cancer Res; 76(20); 6030–42. ©2016 AACR.