Frailty and Caenorhabditis elegans as a Benchtop Animal Model for Screening Drugs Including Natural Herbs

Caenorhabditis elegans has been used in research for years to clarify the genetic cascades and molecular mechanisms of aging, longevity, and health span. Health span is closely related to frailty; however, frailty has a different concept and is evaluated using various parameters in humans, such as Fried's Frailty Criteria. The C. elegans model has several advantages when performing a chemical screen to identify drug candidates. Several mouse models of frailty were recently developed, including a homozygous IL-10 knockout. These mouse models are useful for understanding human frailty; however, they are not appropriate for primary drug screening because they require large spaces, expensive cost, and time consuming assessments. Therefore, a combination of these models may be a promising tool for discovering drugs and understanding the mechanisms of frailty. In addition, natural products, and herbs are attractive sources of novel drugs with pharmacological activity and low toxicity, in fact, over 60% of currently-available drugs are estimated to be related to natural compounds. In this review, the possibility of identifying natural agents (i.e., herb extracts and compounds) that could improve frailty are proposed, and the advantages and limitations of these models are also discussed

Gastroprotective effect of n-butanol fractions from Lumnitzera racemosa leaves against indomethacin induced ulcer in Wistar rats

Phytoconstituents from plants serve as a safe replacement for synthetic molecules in drug production. Lumnitzera racemosa Willd., commonly called white-flowered black mangrove, is used in folk medicine to treat inflammation and other diseases. Here, we evaluated the antiulcer activity of two fractions (LR-B-4-11 and LR-B-4-12) of n-butanol (n-BuOH) fractions of L. racemosa leaves at the doses of 50 and 100 mg/kg, body wt. against indomethacin induced gastric mucosal injury in Wistar rats. The rats were dissected and their stomachs were inspected macroscopically to diagnose hemorrhagic lesions in the gastric and fundic mucosa. Administration of the fractions at doses of 50 and 100 mg/kg body wt., demonstrated a significant reduction in the indomethacin induced gastric erosion when compared to the control. The lower dose of LR-B-4-11 fraction (50 mg/kg) resulted in better inhibition of indomethacin induced gastric ulcer as compared to the control. Histological studies of the fundic and gastric mucosa reported that indomethacin led to mucosal degeneration, ulceration, and migration of numerous inflammatory cells throughout the section. On the other hand, pretreated groups with n-BuOH fractions demonstrated substantial regeneration of the mucosal layer and significant prevention of hemorrhage and edema occurrenc

Histomorphometric study of ethanolic extract of Graptophyllum pictum (L.) Griff. Leaves on croton oil-induced hemorrhoid mice: A Javanese traditional anti-hemorrhoid herb

Ethnopharmacology relevance Graptophyllum pictum (L.) Griff., known as “handeuleum” in West Java and “Daun Ungu” in Indonesia, is traditionally used to cure hemorrhoids. Aim of the study The purpose of this study is to prove its effectiveness scientifically using anorectal histological parameters in Croton oil-induced hemorrhoid mice. Materials and methods In vivo tests were performed by observing histomorphologic changes in mice anorectal tissue induced by croton oil. In addition, in vitro assay was performed for evaluating antioxidant activity, astringency property, and hemostasis-associated activity. The antioxidant activity was measured using a DPPH radical scavenging assay. The total flavonoid and phenolic contents were also determined spectrophotometrically. Results The in vivo assay showed that the oral-topical combination use of the ethanolic extract of G. pictum leaves demonstrated significant improvement on the croton oil-induced anorectal damage better than the single application by oral or topical application. Conclusion These results showed that G. pictum has potent anti hemorrhoid activity, especially for the combinational use of oral and topical administration

New methyl threonolactones and pyroglutamates of Spilanthes acmella

[Objective] Spilanthes acmella is a medicinal plant that distributed in the tropical and subtropical regions with rich source of therapeutic and medicinal constituents. The main constituents, "spilanthol” and “ acmellonate”, are used to reduce the pain associated with toothaches and induce saliva secretion. It is also used traditionally as treatment of rheumatism, tongue paralysis, antipyretic, sore throat, and gum infections [1]. It contains phytosterols, essential oils, sesquiterpenes, α and β-bisabolenes and cadinenes, flavonoid glucoside and a mixture of long chain hydrocarbons. In recent years, other bioactive metabolites have been isolated as vanillic acid, trans-ferulic acid, trans-isofcrulic acid, scopolelin, 3-acetylaleuritolic acid and β-sitostenone[2], [Methods] The aerial parts of Spilanthes acmella were collected in Purwodadi, Indonesia, then extracted with methanol. The obtained methanol extract was concentrated and partitioned with n-hexane, ethyl acetate, and 1-butanol. [Results] On investigation of the 1-butanol layer of this plant, a new methyl threonolactone glucoside (1), a new methyl threonolactone fructofuranoside (2) and two new pyroglutamates (3, 4) along with 2-C-methyl-D-threono-1,4-lactone (5), 2-deoxy-D-ribono-1,4-lactone (6), methylpyroglutamate (7), dendranthemoside A (8), dendranthemoside B (9), ampelopsisionoside (10),icariside B2 (11), benzyl-α-L-arabinopyranosyl-( l-6)-β-D-glucopyranoside (12) and chicoriin (13) were isolated by various chromatographic techniques such as silica gel, ODS column chromatography and HPLC. The structures of these compounds were determined as follows by spectrometric analysis (UV, IR, ID- and 2D-NMR, and HR-ESI-MS)

New Isolinariins C, D and E, Flavonoid Glycosides from Linaria japonica

Three new flavonoid glycosides named isolinariins C, D and E (1–3), two known flavonoid glycosides (4,5) and three known flavonoids (6–8) were isolated from the whole plant of Linaria japonica. The structures of these compounds were determined mainly by spectroscopic analyses. The bioactivities of these isolated compounds were evaluated for their inhibitory activities against human cell line A549, collagenase, and advanced glycation end product (AGE) formation. Among the isolated compounds, isolinariins C, D and E (1, 2 and 3) showed inhibition toward AGE formation (IC50 values of 34.8, 35.0 and 19.5 µM, respectively). And linariin (4), pectolinarin (5) and luteolin (8) were found to be active against collagenase with IC50 values of 79.4, 78.6 and 40.5 µM, respectively, without significant cytotoxicity at these concentrations

Synthesis, In Silico Study, Antibacterial and Antifungal Activities of N-phenylbenzamides

Antibiotic and antifungal resistance problems have been prevalent in recent decades. One of the efforts to solve the problems is to develop new medicines with more potent antibacterial and antifungal activity. N-phenylbenzamides have the potential to be developed as antibacterial and antifungal medicine. This study aimed to synthesize N-phenylbenzamides and evaluate their in silico and in vitro antibacterial and antifungal activities. The in silico studies conducted absorption, distribution, metabolism, excretion and toxicity (ADMET) predictions along with molecular docking studies. ADMET predictions used pkCSM software online, while the docking studies used MVD software (Molegro ® Virtual Docker version 5.5) on Aminoglycosid-2 ”-phosphotransferase-IIa (APH2 ”-IIa) enzyme with protein data bank (PDB) ID code 3HAV as antibacterial and aspartic proteinases enzyme (Saps) with PDB ID code 2QZX as an antifungal. In vitro, antibacterial and antifungal tests were carried out using the zone of inhibition (ZOI) method. The five N-phenylbenzamides (3a–e) were successfully synthesized with a high yield. Based on in silico and in vitro studies, compounds 3a–e have antibacterial and antifungal activities, where they can inhibit the growth of Gram-positive bacteria (Staphylococcus aureus), Gram-negative (Escherichia coli), and Candida albicans. Therefore, compounds 3a–e can be developed as a topical antibacterial and antifungal agent

ACUTE TOXICITY ASSESSMENT OF GRAPTOPHYLLUM PICTUM (L.) GRIFF. LEAVES ETHANOLIC EXTRACT AND ITS NANOFORMULATIONS: COMPARATIVE STUDY OF PHYTOSOME AND CYCLODEXTRIN INCLUSION COMPLEX

Graptophyllum pictum (L.) Griff has been used in traditional medicine to treat various diseases and shows great potential for clinical use, but is often limited by poor oral bioavailability and lack of information regarding its safety. In this study, the herbal extract was developed into two forms e.g., phytosome and cyclodextrin complex in order to enhance its bioavailability. This study also examines the toxicity of G. pictum leaves ethanolic extract (GPLE) and its nanoformulations. The GPLE phytosome (GPLE-P) was formed using hydration method. The GPLE cyclodextrin inclusion complex (GPLECDIC) was produced through co-precipitation methods. Both formulations produced vesicle in nanometer size. The formation of the vesicles was confirmed through FT-IR and differential scanning calorimetry (DSC) analysis. The in vitro toxicity test showed that GPLE and GPLE-P caused erythrocyte morphological changes at 500 μg/mL, while GPLE-CDIC at 250 μg/mL. Oral administration of all formulations did not cause any erythrocyte morphological changes. The complete blood cell analysis showed no significant difference in the number of blood components from the untreated group compared to the treated group. Both formulations can be safely administered orally without any immediate unwanted effect

Iridoid glucoside, (3R)-oct-1-en-3-ol glycosides, and phenylethanoid from the aerial parts of Caryopteris incana

Eleven compounds of interest were isolated from the aerial parts of Caryopteris incana, specifically a new acyl derivative (3) of 8-O-acetylharpagide, two new (3R)-oct-1-en-3-ol glycosides (5, 6), and 6-O-caffeoylphlinoside A (11) along with seven known compounds, 8-O-acetylharpagide (1), 6'-O-p-coumaroyl-8-O-acetylharpagide (2), (3R)-oct-1-en-3-ol (matsutake alcohol) O-alpha-l-arabinopyranosyl-(1aEuro(3) -> 6')-O-beta-d-glucopyranoside (4), apigenin 7-O-neohesperidinoside (7), 6'-O-caffeoylarbutin (8), and two phenylethanoids, leucosceptoside A (9) and phlinoside A (10). This paper deals with structural elucidation of the new compounds