Natural anti-neuroinflammatory inhibitors in vitro and in vivo from Aglaia odorata.

Fifty compounds including seven undescribed (1, 13, 18-20, 30, 31) and forty-three known (2-12, 14-17, 21-29, 32-50) ones were isolated from the extract of the twigs and leaves of Aglaia odorata with anti-neuroinflammatory activities. Their structures were determined by a combination of spectral analysis and calculated spectra (ECD and NMR). Among them, compounds 13-25 were found to possess tertiary amide bonds, with compounds 16, 17, and 19-21 existing detectable cis/trans mixtures in 1H NMR spectrum measured in CDCl3. Specifically, the analysis of the cis-trans isomerization equilibrium of tertiary amides in compounds 19-24 was conducted using NMR spectroscopy and quantum chemical calculations. Bioactivity evaluation showed that the cyclopenta[b]benzofuran derivatives (2-6, 8, 10, 12) could inhibit nitric oxide production at the nanomolar concentration (IC50 values ranging from 2 to 100 nM) in lipopolysaccharide-induced BV-2 cells, which were 413-20670 times greater than that of the positive drug (minocycline, IC50 = 41.34 µM). The cyclopenta[bc]benzopyran derivatives (13-16), diterpenoids (30-35), lignan (40), and flavonoids (45, 47, 49, 50) also demonstrated significant inhibitory activities with IC50 values ranging from 1.74 to 38.44 µM. Furthermore, the in vivo anti-neuroinflammatory effect of rocaglaol (12) was evaluated via immunofluorescence, qRT-PCR, and western blot assays in the LPS-treated mice model. The results showed that rocaglaol (12) attenuated the activation of microglia and decreased the mRNA expression of iNOS, TNF-α, IL-1ß, and IL-6 in the cortex and hippocampus of mice. The mechanistic study suggested that rocaglaol might inhibit the activation of the NF-κB signaling pathway to relieve the neuroinflammatory response.

Alkylphthalides with intracellular triglyceride metabolism-promoting activity from the rhizomes of Cnidium officinale Makino.

Methanol extract of the Cnidium officinale Makino rhizome, which is used as a crude drug Cnidium Rhizome (Cnidii Rhizoma; "Senkyu" in Japanese) and is listed in the Japanese Pharmacopoeia XVIII, showed intracellular triglyceride metabolism-promoting activity in high glucose-pretreated HepG2 cells. Thirty-five constituents, including two new alkylphthalide glycosides, senkyunosides A (1) and B (2), and a neolignan with a new stereoisomeric structure (3), were isolated in the extract. Their stereostructures were elucidated based on chemical and spectroscopic evidence. Among the isolates, several alkylphthalides, (Z)-3-butylidene-7-methoxyphthalide (9) and senkyunolides G (10), H (14), and I (15), and a polyacetylene falcarindiol (26), were found to show significant activity without any cytotoxicity at 10 µM.

α-Glucosidase Inhibitory Components from Garcinia pedunculata Fruits.

From Garcinia pedunculata Roxb. fruits, two undescribed aromatic compounds including a benzofuran and a depsidone derivative, and a new natural product, together with four known compounds were isolated. Through the analysis of spectroscopic data, high resolution mass spectrum and calculated nuclear magnetic resonance, their structures were determined. The α-glucosidase inhibitory activity of the isolates was evaluated. And compound 3 exhibited a moderate inhibitory effect on α-glucosidase. The molecular docking of compound 3 was performed to elucidate the interaction with α-glucosidase.

Morushalunin D, a tri-O-bridged Diels-Alder type adduct from Morus alba var. shalun root cultures and the related precursors.

Three Diels-Alder type adducts (1-3) along with their precursors, including one 2-arylbenzofuran (4) and one stilbene (5), were isolated from the MeOH extract of M. alba var. shalun root cultures. Among them, 1 is a new Diels-Alder type adduct named morushalunin D. The molecular structures of 1-5 were elucidated based on spectroscopic data and comparison with the literatures. Cytotoxic properties of compounds 1-5 were evaluated against murine leukemia P-388 cells. Morushalunin D (1), mulberrofuran T (2), sorocein A (3), moracin M (4), and oxyresveratrol (5) were active, significantly inhibiting the growth of P-388 cells with IC50 values of 0.5, 1.0, 0.6, 2.0, and 3.3 µg/ml, respectively.

Dieckol Isolated from Eisenia bicyclis Ameliorates Wrinkling and Improves Skin Hydration via MAPK/AP-1 and TGF-ß/Smad Signaling Pathways in UVB-Irradiated Hairless Mice.

Repetitive exposure to ultraviolet B (UVB) is one of the main causes of skin photoaging. We previously reported that dieckol isolated from Eisenia bicyclis extract has potential anti-photoaging effects in UVB-irradiated Hs68 cells. Here, we aimed to evaluate the anti-photoaging activity of dieckol in a UVB-irradiated hairless mouse model. In this study, hairless mice were exposed to UVB for eight weeks. At the same time, dieckol at two doses (5 or 10 mg/kg) was administered orally three times a week. We found that dieckol suppressed UVB-induced collagen degradation and matrix metalloproteinases (MMPs)-1, -3, and -9 expression by regulating transforming growth factor beta (TGF-ß)/Smad2/3 and mitogen-activated protein kinases (MAPKs)/activator protein-1 (AP-1) signaling. In addition, dieckol rescued the production of hyaluronic acid (HA) and effectively restored the mRNA expression of hyaluronan synthase (HAS)-1/-2 and hyaluronidase (HYAL)-1/-2 in UVB-irradiated hairless mice. We observed a significant reduction in transepidermal water loss (TEWL), epidermal/dermal thickness, and wrinkle formation in hairless mice administered dieckol. Based on these results, we suggest that dieckol, due to its anti-photoaging role, may be used as a nutricosmetic ingredient for improving skin health.

Design, Semisynthesis, Insecticidal and Antibacterial Activities of a Series of Marine-Derived Geodin Derivatives and Their Preliminary Structure-Activity Relationships.

To enhance the biological activity of the natural product geodin (1), isolated from the marine-derived fungus Aspergillus sp., a series of new ether derivatives (2-37) was designed and semisynthesized using a high-yielding one-step reaction. In addition, the insecticidal and antibacterial activities of all geodin congeners were evaluated systematically. Most of these derivatives showed better insecticidal activities against Helicoverpa armigera Hübner than 1. In particular, 15 showed potent insecticidal activity with an IC50 value of 89 µM, comparable to the positive control azadirachtin (IC50 = 70 µM). Additionally, 5, 12, 13, 16, 30 and 33 showed strong antibacterial activity against Staphylococcus aureus and Aeromonas salmonicida with MIC values in the range of 1.15-4.93 µM. The preliminary structure-activity relationships indicated that the introduction of halogenated benzyl especially fluorobenzyl, into 1 and substitution of 4-OH could be key factors in increasing the insecticidal and antibacterial activities of geodin.

Mitigative Effects of PFF-A Isolated from Ecklonia cava on Pigmentation in a Zebrafish Model and Melanogenesis in B16F10 Cells.

Melanin synthesis is a defense mechanism that prevents skin damage, but excessive accumulation of melanin occurs in the skin in various reactions such as pigmentation, lentigines, and freckles. Although anti-melanogenic effects have been demonstrated for various naturally occurring marine products that inhibit and control tyrosinase activity, most studies have not been extended to in vivo applications. Phlorofucofuroeckol-A (PFF-A, 12.5-100 µM) isolated from Ecklonia cava has previously been shown to have tyrosinase-mitigative effects in B16F10 cells, but it has not been evaluated in an in vivo model, and its underlying mechanism for anti-melanogenic effects has not been studied. In the present study, we evaluated the safety and efficacy of PFF-A for anti-melanogenic effects in an in vivo model. We selected low doses of PFF-A (1.5-15 nM) and investigated their mitigative effects on pigmentation stimulated by α-MSH in vivo and their related-mechanism in an in vitro model. The findings suggest that low-dose PFF-A derived from E. cava suppresses pigmentation in vivo and melanogenesis in vitro. Therefore, this study presents the possibility that PFF-A could be utilized as a new anti-melanogenic agent in the cosmeceutical industries.

Citreobenzofuran D-F and Phomenone A-B: Five Novel Sesquiterpenoids from the Mangrove-Derived Fungus Penicillium sp. HDN13-494.

Five new sesquiterpenoids, citreobenzofuran D-F (1-3) and phomenone A-B (4-5), along with one known compound, xylarenone A (6), were isolated from the culture of the mangrove-derived fungus Penicillium sp. HDN13-494. Their structures were deduced from extensive spectroscopic data, high-resolution electrospray ionization mass spectrometry (HRESIMS), and electronic circular dichroism (ECD) calculations. Furthermore, the absolute structures of 1 were determined by single-crystal X-ray diffraction analysis. Citreobenzofuran E-F (2-3) are eremophilane-type sesquiterpenoids with rare benzofuran frameworks, while phomenone A (4) contains a rare thiomethyl group, which is the first report of this kind of sesquiterpene with sulfur elements in the skeleton. All the compounds were tested for their antimicrobial and antitumor activity, and phomenone B (5) showed moderate activity against Bacillus subtilis, with an MIC value of 6.25 µM.

Potential of Usnic Acid Compound from Lichen Genus Usnea sp. as Antidiabetic Agents.

Lichen Usnea sp. is potential as a new natural medicine. This study report isolation of secondary metabolites from lichen Usnea sp. and α-glucosidase inhibitory, which is potential as an antidiabetic agent. Lichen powder was macerated using methanol, separated using column chromatography gravity and thin-layer chromatography. The crystalline was isolated and purified by the recrystallization process for obtaining pure compound. The isolated compound was determined using FTIR and NMR spectroscopy (1H and 13C). The results showed that the isolated compound was yellow needle crystals. Based on the spectra data interpretation, it was obtained usnic acid compound with the molecular formula of C18H16O7. The α-glucosidase inhibitory activity test showed that the usnic acid had activity in inhibiting the α-glucosidase enzyme with an IC50 value of 106.78 µg/mL. The usnic acid from Usnea sp. has a very good impact on the source of natural compounds as an antidiabetic drug in the future.

In Vitro and In Vivo Photoprotective Effects of (-)-Loliode Isolated from the Brown Seaweed, Sargassum horneri.

Skin is the largest organ of humans. Overexposure to ultraviolet (UV) is the primary environmental factor that causes skin damage. The compound, (-)-loliode, isolated from the brown seaweed Sargassum horneri, showed strong antioxidant and anti-inflammatory activities in in vitro and in vivo models. To further explore the potential of (-)-loliode in cosmetics, in the present study, we investigated the photoprotective effect of (-)-loliode in vitro in skin cells and in vivo in zebrafish. The results indicated that (-)-loliode significantly reduced intracellular reactive oxygen species (ROS) level, improved cell viability, and suppressed apoptosis of UVB-irradiated human keratinocytes. In addition, (-)-loliode remarkably attenuated oxidative damage, improved collagen synthesis, and inhibited matrix metalloproteinases expression in UVB-irradiated human dermal fibroblasts. Furthermore, the in vivo test demonstrated that (-)-loliode effectively and dose-dependently suppressed UVB-induced zebrafish damage displayed in decreasing the levels of ROS, nitric oxide, lipid peroxidation, and cell death in UVB-irradiated zebrafish. These results indicate that (-)-loliode possesses strong photoprotective activities and suggest (-)-loliode may an ideal ingredient in the pharmaceutical and cosmeceutical industries.

The benzofuran glycosides from the fruits of Psoralea corylifolia L.

Six new glucosides of benzofuran (1-6), together with three known glucosides of benzofuran (8, 9, 14), nine flavonoids (12, 13, 15, 18, 19, 20, 21, 22 and 24), three coumarins (16, 17, 23) and four other-typic compounds (7, 10, 11 and 25) were isolated from the fruits of Psoralia corylifolia L. Their structures were elucidated by extensive spectroscopic methods. The biosynthesis pathway of benzofuran system was discussed. Besides, all isolated compounds and additional ring-opening derivatives of psoralen/isopsoralen (P-1, P-2, IP-1 and IP-2) were assayed for inhibition of nitric oxide (NO) production on lipopolysaccharides-induced RAW 264.7 macrophage cells. The results of the assay showed that the glycosides showed weaker or no effects, while most isolated non-glycoside compounds showed moderate or high activities. And the structure-activity relationships of non-glycoside compounds were discussed.

Rhytidhylides A and B, Two New Phthalide Derivatives from the Endophytic Fungus Rhytidhysteron sp. BZM-9.

Two new phthalide derivatives, rhytidhylides A (1) and B (2), together with ten known compounds (3-12) were isolated from cultures of Rhytidhysteron sp. BZM-9, an endophyte isolated from the leaves of Leptospermum brachyandrum. Their structures were identified by an extensive analysis of NMR, HRESIMS, ECD, and through comparison with data reported in the literature. In addition, the cytotoxic activities against two human hepatoma cell lines (HepG2 and SMMC7721) and antibacterial activities against MRSA and E. coli were evaluated.

Aurones and Flavonols from Coreopsis lanceolata L. Flowers and Their Anti-Oxidant, Pro-Inflammatory Inhibition Effects, and Recovery Effects on Alloxan-Induced Pancreatic Islets in Zebrafish.

(1) Background: Many flavonoids have been reported to exhibit pharmacological activity; a preparatory study confirmed that Coreopsis lanceolata flowers (CLFs) contained high flavonoid structure content; (2) Methods: CLFs were extracted in aqueous methanol (MeOH:H2O = 4:1) and fractionated into acetic ester (EtOAc), normal butanol (n-BuOH), and H2O fractions. Repeated column chromatographies for two fractions led to the isolation of two aurones and two flavonols; (3) Results: Four flavonoids were identified based on a variety of spectroscopic data analyses to be leptosidin (1), leptosin (2), isoquercetin (3), and astragalin (4), respectively. This is the first report for isolation of 2-4 from CLFs. High-performance liquid chromatography (HPLC) analysis determined the content levels of compounds 1-4 in the MeOH extract to be 2.8 ± 0.3 mg/g (1), 17.9 ± 0.9 mg/g (2), 3.0 ± 0.2 mg/g (3), and 10.9 ± 0.9 mg/g (4), respectively. All isolated compounds showed radical scavenging activities and recovery activities in Caco-2, RAW264.7, PC-12, and HepG2 cells against reactive oxygen species. MeOH extract, EtOAc fraction, and 1-3 suppressed NO formation in LPS-stimulated RAW 264.7 cells and decreased iNOS and COX-2 expression. Furthermore, all compounds recovered the pancreatic islets damaged by alloxan treatment in zebrafish; (4) Conclusions: The outcome proposes 1-4 to serve as components of CLFs in standardizing anti-oxidant, pro-inflammatory inhibition, and potential anti-diabetic agents.

Anti-Inflammatory Properties of Longifuran A, a New Benzofuran from the Stems of Amomum longiligulare.

In this study, the following compounds were isolated from the dichloromethane fraction of the stems of Amomum longiligulare and then characterized: a new benzofuran, namely, longifuran A (1); five other phenolic compounds, namely, 4-methoxycinnamic acid (2), 2,5-dimethoxyphenol (3), eudesmic acid (4), 1,7-bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one (5), and 4,4'-dihydroxychalcone (6); and two triterpenoids, namely, 24-methylcycloartan-3ß-ol (7) and 24-methylencycloartan-3ß-ol (8). They were evaluated in terms of their inhibitory effects on NO production in LPS-stimulated RAW 264.7 macrophages. Results indicated that 1 and 5 exhibited promising inhibitory activities against NO generation with IC50 of 10.47±1.02 µM and 8.51±1.14 µM, respectively. Enzymatic assays demonstrated that they remarkably suppressed the secretion of two pro-inflammatory cytokines (i. e., IL-6 and TNF-α). They also dose-dependently inhibited the expression of inducible nitric oxide synthase and cyclooxygenase-2, two important enzymes modulating inflammation. Therefore, 1 and 5 could be targets for the development of new anti-inflammatory therapeutics.

Health promoting benefits of pongamol: An overview.

Plant-derived chemicals are a source of novel chemotherapeutic agents. Throughout the human civilization, these novel chemicals have led to the discovery of new pharmacological active agents. Research on herbal medicine is of great importance, as most of the active agents used for treating numerous diseases are from natural sources, while other agents are either semisynthetic or synthetic. Pongamol, a flavonoid, which is the main constituent of Pongamia pinnata, is one such active agents, which exhibits diverse pharmacological activities. Various in vivo and in vitro studies revealed that pongamol is a potentially active agent, as it exerts anticancer, anti-inflammatory, antioxidant, antimicrobial, and anti-diabetic activities. Accordingly, the aim of the present review was to give an up-to-date overview on the chemistry, isolation, bioavailability, pharmacological activity, and health benefits of pongamol. This review focuses on the medicinal and health promoting activities of pongamol, along with possible mechanisms of action. For this purpose, this review summarizes the most recent literature pertaining to pongamol as a therapeutic agent against several diseases. In addition, the review covers information related to the toxicological assessment and safety of this phytochemical, and highlights the medicinal and folk values of this compound against various diseases and ailments.

Dieckol: a brown algal phlorotannin with biological potential.

Dieckol [C36H22O18], is a naturally occurring phlorotannin found in some brown algal species. Dieckol is gaining more attention in the scientific community for its potential biological activities. It has been exhibited a broad spectrum of therapeutic functions including anti-bacterial, anti-cancer, anti-oxidant, anti-aging, anti-diabetic, neuroprotective, and other medicinal applications. Distinct emphasis has been given to extraction, purification, and biomedical applications of dieckol. This critical review comprises of in vitro, in vivo, and in silico biological properties of dieckol. An attempt has been made to evaluate the effectiveness, therapeutical application, and mechanism of dieckol against various diseases. The pharmacological significance, current status and the dosage of multifunctional dieckol and its mechanisms have been discussed in this review. Dieckol plays an important role in apoptosis induction via inhibiting the PI3K, AKT, mTOR and FAK signaling molecules. Dieckol remarkably inhibited the lipid accumulation in high fat diet induced animal models. Dieckol, a multifaceted compound will be beneficial in attenuating the action of various diseases and it could be a potential pharmaceutical and nutraceutical compound. Therefore, the combined effects of dieckol with existing drugs and natural compounds will be studied in future to optimize its benefits. Besides limited information on the toxicological action and dosage administration of dieckol on the human was reported to date. Overall, dieckol is a prospective health-promoting compound for the development of a novel drug against numerous diseases.

Chemical Constituents from the Rhizome of Ligusticum chuanxiong Hort. and Their Nrf2 Inducing Activity.

The rhizome of Ligusticum chuanxiong Hort. has been widely used for the therapy of diabetic nephropathy (DN) in traditional Chinese medicine (TCM). The nuclear transcription factor erythroid 2-related factor (Nrf2) is a potential target for treating DN. The purpose of this research was to study the chemical constituents from the rhizome of L. chuanxiong, evaluate their Nrf2 inducing activity, and find the molecules with potential therapeutic effect against DN. In this study, two new phthalides (1-2) along with twenty-seven known constituents were obtained from the rhizome of L. chuanxiong. Their structures were elucidated through various spectroscopic methods. Twelve constituents, including eight phthalides (2, 5, 6,10-13, 14) and four other compounds (17, 18, 20,28), stimulated NAD(P)H: quinone reductase (QR) activity, suggesting that these bioactive constituents were potential Nrf2 activators. Among the isolated compounds, phthalide levistolide A (LA, 14) upregulated the protein levels of Nrf2, NQO1, and γ-GCS in a dose-dependent manner. Our results implied that the clinical application of the rhizome of L. chuanxiong as an anti-DN drug in TCM might be attributed to the Nrf2 inducing effect of phthalides. Thus, phthalides is a group of promising leading molecules for discovering anti-DN agents.

Personal Glucose Meter for α-Glucosidase Inhibitor Screening Based on the Hydrolysis of Maltose.

As a key enzyme regulating postprandial blood glucose, α-Glucosidase is considered to be an effective target for the treatment of diabetes mellitus. In this study, a simple, rapid, and effective method for enzyme inhibitors screening assay was established based on α-glucosidase catalyzes reactions in a personal glucose meter (PGM). α-glucosidase catalyzes the hydrolysis of maltose to produce glucose, which triggers the reduction of ferricyanide (K3[Fe(CN)6]) to ferrocyanide (K4[Fe(CN)6]) and generates the PGM detectable signals. When the α-glucosidase inhibitor (such as acarbose) is added, the yield of glucose and the readout of PGM decreased accordingly. This method can achieve the direct determination of α-glucosidase activity by the PGM as simple as the blood glucose tests. Under the optimal experimental conditions, the developed method was applied to evaluate the inhibitory activity of thirty-four small-molecule compounds and eighteen medicinal plants extracts on α-glucosidase. The results exhibit that lithospermic acid (52.5 ± 3.0%) and protocatechualdehyde (36.8 ± 2.8%) have higher inhibitory activity than that of positive control acarbose (31.5 ± 2.5%) at the same final concentration of 5.0 mM. Besides, the lemon extract has a good inhibitory effect on α-glucosidase with a percentage of inhibition of 43.3 ± 3.5%. Finally, the binding sites and modes of four active small-molecule compounds to α-glucosidase were investigated by molecular docking analysis. These results indicate that the PGM method is feasible to screening inhibitors from natural products with simple and rapid operations.

Alkyl-benzofuran dimers from Eupatorium chinense with insulin-sensitizing and anti-inflammatory activities.

Five new racemic alkyl-benzofuran dimers, (±)-dieupachinins I-M (1-5), were isolated from the root tubers of Eupatorium chinense, a well-known traditional Chinese medicine for the treatment of diphtheria in Guangdong province. The structures of these compounds, especially the first examples of 12,10'-epoxy dimer dieupachinin I (1), 12-nor-dimer dieupachinin J (2), and 12,12'-dinor-dimer dieupachinin K (3), were elucidated by spectroscopic data analysis. Chiral resolution were further carried out on a cellulose column by HPLC, and compounds 2-5 were successfully separated into two enantiomers, respectively. The absolute configurations of (+)-(2-5) and (-)-(2-5) were established by theoretical ECD calculation. All the compounds were evaluated for insulin-stimulated glucose uptake in C2C12 myotubes and (±)-dieupachinin I (1) exhibited the best activity. Compound 1 enhanced insulin-stimulated glucose uptake via activating the insulin receptor substrate 1/protein kinase B/glycogen synthase kinase-3ß signaling pathway. Moreover, all the isolates were tested for their nitric oxygen (NO) inhibitory effects in lipopolysaccharide-treated RAW264.7 macrophages, and compounds (±)-1, (±)-2, and (±)-4 showed promising inhibitory effects with IC50 values of 6.42 ± 1.85, 6.29 ± 1.94, and 16.03 ± 2.07 µM, respectively. (±)-Dieupachinin I (1) again dose-dependently suppressed LPS-induced expression of inducible NO synthase and nuclear translocation of p65.

Effects of Salvianolic acid B on RNA expression and co-expression network of lncRNAs in brown adipose tissue of obese mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvianolic acid B (SalB) is a polyphenolic compound in Salvia miltiorrhiza Bunge ("Danshen"), which has been largely used in Traditional Chinese Medicine for the treatment of metabolic syndrome, obesity, diabetes, among others. AIM OF STUDY: This study was to investigate the effects of Salvianolic acid B (SalB) on mRNA, lncRNA and circRNA's expression profile in brown adipose tissue (BAT) of obese mice. MATERIALS AND METHODS: High-fat-diet induced obese C57BL/6J mice were treated with SalB (100 mg/kg/day) for 8 weeks. Then, BAT was harvested for RNA-Seq analysis. Differentially expressed mRNAs, lncRNAs and circRNAs were analyzed using the Illumina Hiseq 4000. Following this procedure, bioinformatic tools including Gene ontology (GO), KEGG pathway and lncRNA-mRNA co-network analysis were utilized. Finally, RT-qPCR was performed to validate the differentially expressed RNAs. RESULTS: Compared with control group, 2532 mRNAs, 774 lncRNAs and 25 circRNAs were differentially expressed in SalB group. Additionally, 40 upregulated and 109 downregulated gene-related pathways were identified in the SalB group. Among them, metabolic pathways showed the highest enrichment coefficient in upregulated genes. Moreover, 54 up-regulated and 626 down-regulated coding mRNAs associated with lncRNA-Hsd11b1 and lncRNA-Vmp1. CONCLUSIONS: SalB may play an anti-obesity role by adjusting the expression of mRNAs correlated with inflammatory response and energy metabolism through regulating the expression of lncRNA-Hsd11b1. The findings of this research provide new directions to study the mechanisms of SalB, and would open therapeutic avenues for the treatment of obesity.