Huai-Rong Luo

Protective effects of triterpenoids from Ganoderma resinaceum on H2O2-induced toxicity in HepG2 cells

Ganoderma resinaceum Boud. (Polyporeseae) has long been used for antioxidant, immunoregulation and liver protection. From the fruiting bodies of G. resinaceum, eight new lanostanoids, lucidones D-G (1-4), 7-oxo-ganoderic acid Z2 (5), 7-oxo-ganoderic acid Z3 (6), ganoderesin A (7), and ganoderesin B (8), together with six known lanostanoids (9-14) were isolated. The structures of new compounds were elucidated through extensive spectroscopic analysis. In an in vitro model, ganoderesin B (8), ganoderol B (10) and lucidone A (11) showed inhibitory effects against the increase of ALT and AST levels in HepG2 cells induced by H2O2 compared to a control group in the range of their maximum non-toxic concentration (MNTC). However, compounds 8, 10 and 11 displayed no anti-oxidant activities by DPPH assay. Meanwhile, activation for PXR (Pregnane X Receptor) of ganoderesin B (8), ganoderol B (10) and lucidone A (11) was evaluated; ganoderol (10) exhibited a vital activation for PXR-induced CYP3A4 expression. These results suggested that GTs (Ganoderma triterpenoids) exhibited hepatoprotective activities by lowering ALT and AST levels.

Aspirin extends the lifespan of Caenorhabditis elegans via AMPK and DAF-16/FOXO in dietary restriction pathway.

Aspirin has been revealed to have many beneficial effects for health since it was discovered as a nonsteroidal anti-inflammatory drug (NSAID) to treat pain and inflammation. Here, we investigated the molecular mechanism of aspirin on the lifespan extension of Caenorhabditis elegans. Our results showed that aspirin could extend the lifespan of C. elegans, and increase its health span and stress resistance. The extension of lifespan by aspirin requires DAF-16/FOXO, AMPK, and LKB1, but not SIR-2.1. Aspirin could not extend the lifespan of the mutants of eat-2, clk-1, and isp-1. Aspirin could marginally extend the lifespan of long-live insulin-like receptor mutant daf-2(e1370) III. Taken together, aspirin might act through a dietary restriction-like mechanism, via increasing the AMP:ATP ratio and activating LKB1, subsequently activating AMPK, which stimulates DAF-16 to induce downstream effects through a DAF-16 translocation independent manner.

Hypercohin A, a new polycyclic polyprenylated acylphloroglucinol possessing an unusual bicyclo[5.3.1]hendecane core from Hypericum cohaerens

Hypercohin A (1), an unprecedented polycyclic polyprenylated acylphloroglucinol featuring with an unusual bicyclo[5.3.1]hendecane core, was isolated from Hypericum cohaerens. Its structure and absolute configurations were elucidated by extensive NMR methods and crystal X-ray diffractions of its p-bromobenzoate ester (2).

Lycopalhine A, a novel sterically congested Lycopodium alkaloid with an unprecedented skeleton from Palhinhaea cernua

A novel sterically congested Lycopodium alkaloid named lycopalhine A (1) that possesses a fused hexacyclic (5/5/5/6/6/6) ring system comprising a 5,9-diaza-tricyclo[6.2.1.0(4,9)]undecane moiety and a tricyclo[5.2.1.0(4,8)]decane moiety was isolated from Palhinhaea cernua L. The structure and absolute configuration were determined by spectroscopic and computational methods.

Isolation and bioactivity evaluation of terpenoids from the medicinal fungus Ganoderma sinense.

A new pentanorlanostane, ganosineniol A (1), eight new lanostane triterpenoids, ganosinoside A (2), ganoderic acid Jc (3), ganoderic acid Jd (4), ganodermatetraol (5), ganolucidic acid γa (6), ganolucidate F (7), ganoderiol J ( 8), and methyl lucidenate Ha ( 9), and a new sesquiterpenoid, ganosinensine (10), together with eleven known triterpenoids (11- 21), were isolated from the fruiting bodies of the fungus Ganoderma sinense. Chemical structures were determined based on spectroscopic evidence, including 1D, 2D NMR, and mass spectral data. Furthermore, all isolates were tested for cytotoxic activity and induction ability of hPXR-mediated CYP3A4 expression. Among them, ganoderic acid Jc (3) displayed selective inhibitory activity against HL-60 cells (IC₅₀ = 8.30 µM), and ganoderiol E (11) exhibited selective cytotoxic activity against MCF-7 cells (IC₅₀ = 6.35 µM). Meanwhile, compounds 5, 7, and ganolucidic acids B and C (19, 20) showed induction ability of hPXR-mediated CYP3A4 expression.

Drug Absorption Efficiency in Caenorhbditis elegans Delivered by Different Methods

Background Caenorhbditis elegans has being vigorously used as a model organism in many research fields and often accompanied by administrating with various drugs. The methods of delivering drugs to worms are varied from one study to another, which make difficult in comparing results between studies. Methodology/Principal Findings We evaluated the drug absorption efficiency in C. elegans using five frequently used methods with resveratrol with low aqueous solubility and water-soluble 5-Fluoro-2′-deoxyuridine (FUDR) as positive compounds. The drugs were either applied to the LB medium with bacteria OP50, before spreading onto Nematode Growth Medium (NGM) plates (LB medium method), or to the NGM with live (NGM live method) or dead bacteria (NGM dead method), or spotting the drug solution to the surface of plates directly (spot dead method), or growing the worms in liquid medium (liquid growing method). The concentration of resveratrol and FUDR increased gradually within C. elegans and reached the highest during 12 hours to one day and then decreased slowly. At the same time point, the higher the drug concentration, the higher the metabolism rate. The drug concentrations in worms fed with dead bacteria were higher than with live bacteria at the same time point. Consistently, the drug concentration in medium with live bacteria decreased much faster than in medium with dead bacteria, reach to about half of the original concentration within 12 hours. Conclusion Resveratrol with low aqueous solubility and water-soluble FUDR have the same absorption and metabolism pattern. The drug metabolism rate in worms was both dosage and time dependent. NGM dead method and liquid growing method achieved the best absorption efficiency in worms. The drug concentration within worms was comparable with that in mice, providing a bridge for dose translation from worms to mammals.

Germacrane-Type Sesquiterpenoids from the Roots of Valeriana officinalis var. latifolia

Eight new germacrane-type sesquiterpenoids, volvalerenals A-E (2-6) and volvalerenic acids A-C (7-9), along with four known compounds, were isolated from a chloroform extract of the roots of Valeriana officinalis var. latifolia. The structures and relative configurations of 2-9 were elucidated on the basis of spectroscopic data interpretation. The effects of all compounds isolated on acetylcholinesterase were evaluated.

Lyonin A, a New 9,10‐Secograyanotoxin from Lyonia ovalifolia

Phytochemical studies on the branches and leaves of Lyonia ovalifolia yielded a new grayanane diterpenoid, lyonin A (1), together with two known compounds, secorhodomollolides A and D (2 and 3, resp.). The structure of 1 was elucidated by combination of 1D‐ and 2D‐NMR, and MS analyses. Compound 1 turned out to be a new, highly O‐acylated grayanane diterpenoid, of which ring B has undergone an oxidative cleavage between C(9) and C(10), yielding a system differing from the previously reported grayanane type with a 5/7/6/5 ring system. Results of the cAMP regulation activity assay showed that compounds 2 and 3 at 50 μM induced a significantly decreased cAMP level in N1E‐115 neuroblastoma cells (p<0.001), indicating neuropharmacological potential.

Volvalerelactones A and B, Two New Sesquiterpenoid Lactones with an Unprecedented Skeleton from Valeriana officinalis var. latifolia

Volvalerelactones A and B (1 and 2), two new sesquiterpenoid lactones with an unprecedented 3/7/6 tricyclic ring system, were isolated from the roots of Valeriana officinalis var. latifolia. Their structures and relative configurations were elucidated by spectroscopic data and single-crystal X-ray diffraction crystallography, and the absolute configuration was assigned by computational methods. The possible biosynthetic pathways of 1 and 2 were also proposed.

Identification and optimization of 2‐aminobenzimidazole derivatives as novel inhibitors of TRPC4 and TRPC5 channels

Transient receptor potential canonical (TRPC) channels play important roles in a broad array of physiological functions and are involved in various diseases. However, due to a lack of potent subtype‐specific inhibitors the exact roles of TRPC channels in physiological and pathophysiological conditions have not been elucidated.