In vivo Anti-Inflammatory and Immunomodulatory Activity of Soft Coral Nephthea sp. from Southeast Sulawesi.

<b>Background and Objective:</b> <i>Nephthea</i> sp., has various biological activities. The study on anti-inflammatory and immunomodulatory of <i>Nephthea</i> sp., from Southeast Sulawesi is still limited. Hence, this study aims to determine the content of secondary metabolite compounds and their pharmacological activities including anti-inflammatory and immunomodulatory. <b>Materials and Methods:</b> <i>Nephthea</i> sp., was collected from Saponda Island and extracted using ethyl acetate. The chemical contents were analyzed by a phytochemical screening test, anti-inflammatory activity by xylene-induced ear edema and immunomodulatory activity using macrophage phagocytic activity (SPA) in experimental animals. <b>Results:</b> The ethyl acetate extract of <i>Nephthea</i> sp., contains flavonoids and steroids. According to the result obtained, the ethyl acetate extract of <i>Nephthea</i> sp., exhibited anti-inflammatory and immunomodulatory activity <i>in vivo</i>. The EAN 0.2 demonstrated the highest potency and showed no significant difference compared to diclofenac sodium at a concentration of 0.15 mg mL¹ (p>0.05) with the highest percentage edema inhibition as in xylene-induced ear edema. In addition, EAN 0.2 exhibited a similar result in increasing SPA compared to control (p>0.05). Both assays showed significant differences with negative control in this study (p<0.05). <b>Conclusion:</b> Soft coral <i>Nephthea</i> sp., can be a potential candidate as an anti-inflammatory and immunomodulatory agent.

Effect of Immunomodulating Extract and Some Isolates from Etlingera rubroloba A.D. Poulsen Fruits on Diabetic Patients with Tuberculosis.

Diabetes mellitus (DM) is a disease easily complicated by tuberculosis (TB) due to impaired function of the innate immune response. The successes of the discovery of immunomodulatory compounds needs to be continued to introduce new insights into the innate immune response. In previous studies, plant compounds of Etlingera rubroloba A.D. Poulsen (E.rubroloba) were demonstrated to have potential as an immunomodulators. This study aims to isolate and identify the structure of the compounds of E.rubroloba fruit that could effectively improve the function of the innate immune response in individuals with DM infected with TB. The isolation and purification of the compounds of the E.rubroloba extract were carried out by radial chromatography (RC) and thin-layer chromatography (TLC). Identification of the isolated compound structures was determined by measuring the proton (1H) and carbon (13C) nuclear magnetic resonance (NMR). In vitro testing was performed on the immunomodulating activity of the extracts and isolated compounds on DM model macrophages infected with TB antigens. This study succeeded at isolating and identifying the structures of two isolate compounds, namely Sinaphyl alcohol diacetat (BER-1), and Ergosterol peroxide (BER-6). The two isolates were more effective as immunomodulators than the positive controls were, which differed significantly (* p < 0.05) at the reducing interleukin-12 (IL-12) levels and Toll-like receptor-2 (TLR-2) protein expression and increasing the human leucocyte antigen-DR (HLA-DR) protein expression in DM infected with TB. The isolated compound was discovered in E. rubroloba fruits, which has been reported to have the potential to be developed as an immunomodulatory agent. Follow-up testing to determine the mechanism and effectiveness of these compounds as immunomodulators for DM patients is required so that they are not susceptible to TB infection.

Antioxidant and Anti-Inflammatory Activity of Ethanol Extract Stem of Etlingera rubroloba A.D. Poulsen.

<b>Background and Objective:</b> <i>Etlingera rubroloba</i> A.D. Poulsen (<i>E. rubroloba</i>) is a plant endemic to South-East Sulawesi which is used empirically by local people as a pain reliever for joints and to increase endurance after typhoid fever. This study aimed to determine the antioxidant and anti-inflammatory activity of the ethanol extract stem of <i>E. rubroloba</i>. <b>Materials and Methods:</b> The stem of the ethanol extract of <i>E. rubroloba</i> with evaluated for antioxidants using the FRAP method and anti-inflammatory activity with the parameter level of Tumor Necrosis Factor-Alpha (TNF-α) <i>in vivo</i> by using 6 groups of rats, namely the normal, the negative (Na-CMC 0.5%), the positive control (Diclofenac sodium) and the ethanol extract group at doses of 200, 300 and 400 mg kg¹ b.wt. <b>Results:</b> The results of this study indicated that the antioxidant activity value of the IC₅₀ ethanol extract was 12.720±0.12 µg mL¹ and ascorbic acid (vitamin C) as a standard control was 3.14±0.12 µg mL¹. The TNF- α normal group (7.83 pg mL¹), negative control (250.92 pg mL¹), positive control (123.66 pg mL¹), treatment group dose 200 (192.20 pg mL¹), 300 (97, 95 pg mL¹) and 400 mg kg¹ b.wt. (28.78 pg mL¹). <b>Conclusion:</b> This study concluded that the ethanol extract of the stem of <i>E. rubroloba</i> has a very strong antioxidant activity and is an anti-inflammatory which is the best in reducing levels of TNF-α at a dose of 400 mg kg¹ b.wt.

Xanthone Biosynthetic Pathway in Plants: A Review.

Xanthones are secondary metabolites rich in structural diversity and possess a broad array of pharmacological properties, such as antitumor, antidiabetic, and anti-microbes. These aromatic compounds are found in higher plants, such as Clusiaceae, Hypericaceae, and Gentianaceae, yet their biosynthetic pathways have not been comprehensively updated especially within the last decade (up to 2021). In this review, plant xanthone biosynthesis is detailed to illuminate their intricacies and differences between species. The pathway initially involves the shikimate pathway, either through L-phenylalanine-dependent or -independent pathway, that later forms an intermediate benzophenone, 2,3',4,6-tetrahydoxybenzophenone. This is followed by a regioselective intramolecular mediated oxidative coupling to form xanthone ring compounds, 1,3,5-trihydroxyxanthone (1,3,5-THX) or 1,3,7-THX, the core precursors for xanthones in most plants. Recent evidence has shed some lights onto the enzymes and reactions involved in this xanthone pathway. In particular, several biosynthetic enzymes have been characterized at both biochemical and molecular levels from various organisms including Hypericum spp., Centaurium erythraea and Garcinia mangostana. Proposed pathways for a plethora of other downstream xanthone derivatives including swertianolin and gambogic acid (derived from 1,3,5-THX) as well as gentisin, hyperixanthone A, α-mangostin, and mangiferin (derived from 1,3,7-THX) have also been thoroughly covered. This review reports one of the most complete xanthone pathways in plants. In the future, the information collected here will be a valuable resource for a more directed molecular works in xanthone-producing plants as well as in synthetic biology application.

Bioassay Analysis and Molecular Docking Study Revealed the Potential Medicinal Activities of Active Compounds Polygonumins B, C and D from Polygonum minus (Persicaria minor).

Polygonumins B, C and D, derivative compounds of polygonumins A, were isolated from the stem of Polygonum minus. Based on NMR results, the structure of polygonumins derivatives is comprised of four phenylpropanoid units and a sucrose unit, with a similar structure to polygonumins A. However, the structural differences between polygonumins B (1), C (2) and D (3) can be distinguished based on the existence of methoxy, ethanoyl and hydroxyl groups and protons which bind to C-4, C-4' and C-3″. Interestingly, these bioactive compounds showed various medicinal properties based on our investigation on antioxidant, anticholinesterase and anti-HIV-1 protease activities. The IC50 value of DPPH and ABTS (antioxidant activities) was in the following descending order: polygonumins B > polygonumins C > polygonumins A > polygonumins D. In addition, almost similar pattern of antioxidant activity was observed for anti-acetylcholinesterase activity based on its IC50 value in descending order: polygonumins B > polygonumins C > polygonumins D > polygonumins A. On the other hand, polygonumins C and D showed inhibition of HIV-1 protease activity more than the positive control, pepstatin A. Finally, molecular docking studies on AChE and BChE proteins were carried out in order to gain insight into the mode of interactions between these compounds and the active residues for both enzymes. These remarkable findings indicate that these compounds have potential to be developed as targeted drugs for Alzheimer's disease or as anti-HIV drugs.

Molecular docking and molecular dynamics studies of bioactive compounds contained in noni fruit (Morinda citrifolia L.) against human pancreatic α-amylase.

Human pancreatic α-amylase inhibition is currently a promising therapeutic target against type 2 diabetes (DMT2) because it can reduce aggressive digestion of carbohydrates into absorbable monosaccharides. In Indonesia, medicinal plants, e.g. Morinda citrifolia fruit, have been empirically utilized as a blood-sugar reducer, however, the inhibitory activity of compounds in this plant against human pancreatic α-amylase is still limited or none. Therefore, this study aimed to test the interaction of 7 compounds (americanin, asperulosidic acid, damnacanthal, quercetin, rutin, scopoletin, and ursolic acid) contained in noni fruit against human pancreatic α-amylase by molecular docking and molecular dynamics and compared their binding modes with that of acarbose. Results of the molecular docking simulation indicated that the ursolic acid compound possesses the best binding energy (-8.58 kcal/mol) and comparable to that of acarbose (-8.59 kcal/mol). The molecular dynamics study at 100 ns simulation, the values of RMSD, RMSF, the radius of gyration (Rg), the solvent-accessible surface area (SASA), principal component analysis (PCA), and MM-PBSA binding free energy were stable and identical to those of acarbose. It could be concluded that ursolic acid might be potential in inhibiting human pancreatic α-amylase, thus, potential to be developed as an anti-DMT2 drug candidate. Communicated by Ramaswamy H. Sarma.

Suppression of Proinflammatory Cytokines by Etlingera alba (A.D.) Poulsen Rhizome Extract and Its Antibacterial Properties.

Etlingera alba is one of the Etlingera plants that has not been studied intensively. Plants that belong to the same genus have similar constituents and pharmacological activities. Thus, we aim to investigate the chemical composition and pharmacological activities, namely, anti-inflammatory and antibacterial properties, of E. alba rhizome extract (EA). The chemical constituent was detected using the test tube method. The inflammatory model rats were obtained by inducing them with 1% carrageenan, and their palm edema volume and cytokine levels, namely, IL-6, IL-12, and TNF-α, were measured. Antibacterial activity was performed with broth microdilution. The phytochemical screening of EA was detecting alkaloids, flavonoids, tannins, steroids, and phenols. The EA has anti-inflammatory activity by reducing the palms' edema volume and cytokine levels (IL-6, IL-12, and TNF-α), and the optimal concentration was 400 mg/kg body weight (BW). On the other hand, EA also exhibited antibacterial properties against E. coli and S. enterica. In conclusion, similar to other Etlingera plants, EA also demonstrates pharmacological activities, namely, anti-inflammatory and antibacterial properties.

Heavy metal bioaccumulation in mangrove ecosystem at the coral triangle ecoregion, Southeast Sulawesi, Indonesia.

This study aimed to determine the role of mangroves as a biofilter of heavy metals. The concentrations of heavy metals, namely copper, mercury, cadmium, zinc, and lead, in the mangroves Rhizophora apiculata, Ceriops tagal, Bruguiera gymnorrhiza, Lumnitzera racemosa, Xylocarpus granatum, Sonneratia alba, and Bruguiera parviflora at RAWN Park were determined using a Flame atomic absorption spectrophotometer. High concentrations of Cu (83.85µgg-1) and Hg (0.52µgg-1) were found in the tissues of L. racemosa, while high concentrations of Cd (10.81µgg-1), Zn (70.41µgg-1), and Pb (1.36µgg-1) were found in the tissues of B. gymnorrhiza, B. parviflora and C. tagal, respectively. The translocation and bioaccumulation factors of heavy metals by mangroves showed a variety of trends, which indicated the different partitioning and uptake capability of heavy metals in the tissues of various mangrove species. Thus, maintaining high diversity of mangroves is crucial to ensure the health and productivity of coastal zones.

Inhibitory effect of triterpenoids from Dillenia serrata (Dilleniaceae) on prostaglandin E2 production and quantitative HPLC analysis of its koetjapic acid and betulinic acid contents.

The crude methanol extracts and fractions of the root and stem barks of Dillenia serrata Thunb. showed 64% to 73% inhibition on the production of prostaglandin E2 (PGE2) in lipopolysaccharide-induced human whole blood using a radioimmunoassay technique. Three triterpenoids isolated from the root bark of the plant, koetjapic (1), 3-oxoolean-12-en-30-oic (2), and betulinic (3) acids, exhibited significant concentration-dependent inhibitory effects on PGE2 production with IC50 values of 1.05, 1.54, and 2.59 µM, respectively, as compared with the positive control, indomethacin (IC50 = 0.45 µM). Quantification of compounds 1 and 3 in the methanol extracts and fractions were carried out by using a validated reversed-phase high performance liquid chromatography (RP-HPLC) method. The ethyl acetate fraction of the stem bark showed the highest content of both compound 1 (15.1%) and compound 3 (52.8%). The strong inhibition of the extracts and fractions on cyclooxygenase-2 (COX-2) enzymatic activity was due to the presence of their major constituents, especially koetjapic and betulinic acids.

Acuminatol and other antioxidative resveratrol oligomers from the stem bark of Shorea acuminata.

A new resveratrol dimer, acuminatol (1), was isolated along with five known compounds from the acetone extract of the stem bark of Shorea acuminata. Their structures and stereochemistry were determined by spectroscopic methods, which included the extensive use of 2D NMR techniques. All isolated compounds were evaluated for their antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (RSA) and the ß-carotene-linoleic acid (BCLA) assays, and compared with those of the standards of ascorbic acid (AscA) and butylated hydroxytoluene (BHT). All compounds tested exhibited good to moderate antioxidant activity in the DPPH assay (IC50s 0.84 to 10.06 mM) and displayed strong inhibition of ß-carotene oxidation (IC50s 0.10 to 0.22 mM). The isolated compounds were evaluated on the Vero cell line and were found to be non-cytotoxic with LC50 values between 161 to 830 µM.