Molecular dynamics study of stigmasterol and beta-sitosterol of Morinda citrifolia L. towards α-amylase and α-glucosidase.

Previous in vivo studies of Morinda citrifolia (Rubiaceae) reported that the extract inhibited α-amylase and reduced blood glucose levels in streptozotocin-induced diabetes mice. Moreover, molecular docking studies confirmed that ursolic acid and sterol compounds contained in the fruit interacted with important residues in the binding site of α-amylase and α-glucosidase. Our work aimed to study the complex stability of stigmasterol (which has been isolated from the M. citrifolia fruit for the first time) and beta-sitosterol towards α-amylase and α-glucosidase by employing molecular dynamics simulation on GROMACS 2016.3 embedded with the AMBER99SB-ILDN force field. The simulation was carried out for 100 ns at 310 oK. Based on the RMSD and RMSF graphs, the complexes of stigmasterol/α-amylase and stigmasterol/α-glucosidase are more stable compared to acarbose, the known inhibitor of both enzymes. Moreover, beta-sitosterol indicates a better stability complex with α-glucosidase compared to that of acarbose. Interestingly, the affinity of stigmasterol and beta-sitosterol to both enzymes, in terms of the total binding energy, is stronger than that of acarbose. Taken together, stigmasterol and beta-sitosterol in M. citrifolia fruit may have the potency to be developed as α-amylase and α-glucosidase inhibitors.Communicated by Ramaswamy H. Sarma.

Isolation of phenolic compound from Lawsonia inermis and its prediction as anti-diabetic agent using molecular docking and molecular dynamic simulation.

High blood sugar is a defining feature of chronic disease, diabetes mellitus (DM). There are numerous commercially available medications for the treatment of DM. However, managing the patient's glucose levels remain a challenge because of the gradual reduction in beta-cell function and some side effects from the long-term use of various medications. Previous research has shown that the phenolic compound of henna plant (Lawsonia inermis L.) has the potential as anti-diabetic agent since it is able to suppress the digesting of α-amylase enzyme. In these studies, the plant' phenolic compounds have been isolated and characterized using UV, IR, NMR and LC-MS methods. Furthermore, the compound interaction into the active site of the α-amylase enzyme has been analyzed using molecular docking and molecular dynamics, as well as into α-glucosidase enzyme for predicting of the affinities. The results showed that isolated compound has the molecular formula of C15H10O6 with eleven degrees of unsaturation (DBE; double bond equivalence). The DBE value corresponds to the structure of the luteolin compound having an aromatic ring (8), a carbonyl group on the side chain (1) and a ketone ring with (2). The interaction study of the isolated compound with α-amylase and α-glucosidase enzyme using molecular docking compared to the positive control (acarbose) gave binding energy of -8.03 and -8.95 kcal/mol, respectively. The molecular dynamics simulation using the MM-PBSA method, complex stability based on solvent accessible surface area (SASA), root mean square deviation (RMSD), and root mean square fluctuation (RMSF) revealed that the compound has a high affinity for receptors. The characteristics of skin permeability, absorption, and distribution using ADME-Tox model were also well predicted. The results indicate that the phenolic compound isolated from L. inermis leaf was luteolin and it has the potential as an anti-diabetic agent.Communicated by Ramaswamy H. Sarma.

Phytochemical Analysis and Immunomodulatory Potential on Diabetic-Infected Tuberculosis by Fruit Etlingera rubroloba A.D. Poulsen.

<b>Background and Objective:</b> <i> Etlingera rubroloba</i> (<i>E. rubroloba</i>) A.D. Poulsen is an endemic plant in South-East Sulawesi and is a newly discovered species. This plant is expected to have the potential as an immunomodulator in patients with diabetes mellitus (DM), which can prevent tuberculosis infection by increasing the phagocytic function of macrophage cells and interleukin-12 (IL-12) levels. <b>Materials and Methods:</b> Phytochemical analysis of the ethanolic extract of the fruit of <i>E. rubroloba</i> A.D. Poulsen using Liquid Chromatography-Mass Spectrometry (LC-MS/MS) was carried out. The immunomodulatory potential <i>in vivo</i> on BALB/c mice model DM was carried out by oral induction of TB antigen with extract dose, control positive, negative and normal groups. Furthermore, the phagocytic activity of macrophage cells can be seen with a microscope and the levels of IL-12 with the Elisa kit. <b>Results:</b> The results showed the ethanol extract of the fruit of <i>E. rubroloba</i> contained eight chemical compounds and had potential as immunomodulators in BALB/c DM mice induced by TB antigen by increasing the phagocytic activity of macrophage cells and levels of IL-12, which were significantly different from the negative control (p<0.05). <b>Conclusion:</b> The chemical composition of the ethanol extract of the fruit of <i>E. rubroloba</i> has the potential as an immunomodulator in TB antigen-induced DM <i>in vivo</i>.

Phytochemical Screening, Toxicity Activity and Antioxidant Capacity of Ethanolic Extract of Etlingera alba Rhizome.

<b>Background and Objective:</b> <i>Etlingera alba </i>(Blume) A.D. Poulsen is one of the plants of the genus <i>Etlingera</i> which is commonly found in Southeast Sulawesi. The research is still lacking, thus, we assumed other species related to <i>E. alba,</i> specifically from the genus<i> Etlingera</i> that provides antioxidant and radical scavenging activity, namely <i>Etlingera elatior</i> (Jack) R.M. Smith. Thus, this study aimed to assess the antioxidant and toxicity activity as well as its secondary metabolites. <b>Materials and Methods:</b> <i>Etlingera alba</i> rhizome was extracted with 96% ethanol. The radical scavenging activity was assayed with 1,1-diphenyl-2-picrylhydrazyl (DPPH) and antioxidant activity was assayed with 2,2'-azino-bis-[3-ethylbenzothiazoline sulphonate (ABTS) assay for radical cation decolourization<i> in vitro</i>. Both Ascorbic Acid (AA) and Trolox were used as positive control. The secondary metabolites were identified by Thin Layer Chromatography (TLC) and LSMS/MS analyzed the difference between compounds. According to results performed with TLC and LCMS/MS. <b>Results:</b> The extract exhibited antioxidant properties using both DPPH and ABTS method. The LC₅₀ of the extract was 608.42±18.31 mg L¹.<i> Etlingera alba </i>rhizome extract contains alkaloids, flavonoids, terpenoids and steroids. The compounds detected in the extract were E-p-Coumaric acid aschantin, 2-Methoxyanofinic acid, Chavicol-ß-D-glucoside, Myristicanol B, ent-16α,17-Hydroxy-19-kaurenoic acid, 5-Hydroxy-7,8,2'-trimethoxyflavone, Methyl ursolate and Spinasterol. <b>Conclusion:</b> <i>Etlingera alba</i> rhizome contains several compounds that might be responsible for antioxidant activity and the extract itself classified as medium toxic.

Cytotoxic and Antimigration Activity of Etlingera alba (A.D.) Poulsen Rhizome.

Etlingera alba is one of the Etlingera plants that might have anticancer activity. This study aims to investigate the cytotoxic and antimetastatic activity of E. alba rhizome fractions and migration cell assay against MDA-MB-231 cell lines, which are used for triple-negative breast cancer (TNBC) treatment assay. The cytotoxic activity was assayed using CCK-8 assay, while the antimetastatic was assayed using migration cell assay for the fractions A-F. They were followed by LCMS/MS profiling to determine the chemical contents in the most active fraction. According to results obtained, fraction B was the most active fraction for cytotoxic activity with an IC50 value of 65.43 µg/mL, while fraction E was the most active fraction for antimetastasis activity against migration rate doses of 50, 100, and 200 ppm which were 6.80, 3.66, and 3.00%, respectively. Several compounds in fraction B, such as rengyolone, licochalcone A, sugiol, and spinasterol, might have been known to have activity against cancer cells, as well as aschantin and lirioresinol B dimethyl ether from fraction E. In conclusion, the chemical components from E. alba rhizome fractions provided potency for discovering new agents for cancer treatment, specifically for TNBC.

Polygonumins A, a newly isolated compound from the stem of Polygonum minus Huds with potential medicinal activities.

Polygonumins A, a new compound, was isolated from the stem of Polygonum minus. Based on NMR results, the compound's structure is identical to that of vanicoside A, comprising four phenylpropanoid ester units and a sucrose unit. The structure differences were located at C-3″″'. The cytotoxic activity of polygonumins A was evaluated on several cancer cell lines by a cell viability assay using tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The compound showed the highest antiproliferative (p < 0.05) activities against K562 (Human Leukaemia Cell Line), MCF7 (Human breast adenocarcinoma cell line), and HCT116 (Colorectal cancer cells) cells. Cytotoxic studies against V79-4 cells were carried out and showed that polygonumins A was toxic at 50 µg/ml, suggesting that this compound may be used as an anticancer drug without affecting normal cells. Polygonumins A also showed promising activity as an HIV-1 protease inhibitor with 56% relative inhibition. Molecular docking results indicated that the compound possesses high binding affinity towards the HIV protease over the low binding free energy range of -10.5 to -11.3 kcal/mol. P. minus is used in Malaysian traditional medicine for the treatment of tumour cells. This is the first report on the use of P. minus as an HIV-1 protease inhibitor.

Medicinal uses, phytochemistry and pharmacology of Pongamia pinnata (L.) Pierre: a review.

ETHNOPHARMACOLOGICAL RELEVANCE: Pongamia pinnata (L.) Pierre is one of the many plants with diverse medicinal properties where all its parts have been used as traditional medicine in the treatment and prevention of several kinds of ailments in many countries such as for treatment of piles, skin diseases, and wounds. AIM OF THIS REVIEW: This review discusses the current knowledge of traditional uses, phytochemistry, biological activities, and toxicity of this species in order to reveal its therapeutic and gaps requiring future research opportunities. MATERIAL AND METHODS: This review is based on literature study on scientific journals and books from library and electronic sources such as ScienceDirect, PubMed, ACS, etc. RESULTS: Several different classes of flavonoid derivatives, such as flavones, flavans, and chalcones, and several types of compounds including terpenes, steroid, and fatty acids have been isolated from all parts of this plant. The pharmacological studies revealed that various types of preparations, extracts, and single compounds of this species exhibited a broad spectrum of biological activities such as antioxidant, antimicrobial, anti-inflammatory, and anti-diabetic activities. CONCLUSION: The results of several toxicity studies indicated that extracts and single compounds isolated from this species did not show any significant toxicity and did not cause abnormality on some rats' organs. Thus, this plant has a potential to be used as an effective therapeutic remedy due to its low toxicity towards mammalian cells. However, further study on chemical constituents and their mechanisms in exhibiting certain biological activities are needed to understand the full phytochemical profile and the complex pharmacological effects of this plant. In addition, further study on the toxicity of the other compounds isolated from this plant required to be assessed to ensure their eligibility to be used as sources of drugs.

Medicinal property, phytochemistry and pharmacology of several Jatropha species (Euphorbiaceae): a review.

The genus Jatropha (Euphorbiaceae) comprises of about 170 species of woody trees, shrubs, subshrubs or herbs in the seasonally dry tropics of the Old and the New World. They are used in medicinal folklore to cure various diseases of 80% of the human population in Africa, Asia and Latin America. Species from this genus have been popular to cure stomachache, toothache, swelling, inflammation, leprosy, dysentery, dyscrasia, vertigo, anemia, diabetis, as well as to treat HIV and tumor, opthalmia, ringworm, ulcers, malaria, skin diseases, bronchitis, asthma and as an aphrodisiac. They are also employed as ornamental plants and energy crops. Cyclic peptides alkaloids, diterpenes and miscellaneous compounds have been reported from this genus. Extracts and pure compounds of plants from this genus are reported for cytotoxicity, tumor-promoting, antimicrobial, antiprotozoal, anticoagulant, immunomodulating, anti-inflammatory, antioxidant, protoscolicidal, insecticidal, molluscicidal, inhibition AChE and toxicity activities.