Xin-Long Wang

Cochlearols A and B, Polycyclic Meroterpenoids from the Fungus Ganoderma cochlear That Have Renoprotective Activities

(+)- and (-)-cochlearols A (1) and B (2), two meroterpenoids with novel polycyclic skeletons, were isolated from the fruiting bodies of the fungus Ganoderma cochlear. Their structures and stereochemistry were determined by using spectroscopic, computational and single-crystal X-ray diffraction methods. Cochlearol A is a new normeroterpenoid containing a naturally unusual dioxaspiro[4.5]decane motif. Biological studies showed that (-)-2 is a strong inhibitor of p-Smads, exhibiting renoprotective activities in TGF-β1 induced rat renal proximal tubular cells.

Lingzhilactones from Ganoderma lingzhi ameliorate adriamycin-induced nephropathy in mice

ETHNOPHARMACOLOGICAL RELEVANCE Several Ganoderma fungi are well-known for their medical uses to treat cancer, insomnia and kidney disease in East Asia. Triperpenoids and polysaccharides have been considered for a long time to be the major active components of the genus Ganoderma. The present study is to examine the effects of lingzhilactones from G. lingzhi on adriamycin-induced nephropathy in mice. MATERIALS AND METHODS A combination of various chromatography led to the isolation of lingzhilactones A-C, their structures were identified by spectroscopic and computational methods. The intracellular reactive oxygen species (ROS) was detected with the carboxymethyl-H2-dichlorofluorescein diacetate fluoroprobe. The fibrotic markers were analyzed by real-time RT-PCR and Western blot analyses. Detection of SEAP was conducted with the chemiluminescent. Urine albumin was measured using an ELISA assay. Histology and immunohistochemical staining was used to assess fibrotic lesions in mice. RESULTS Three new lingzhilactones A-C (1-3) containing a fused lactone moiety were isolated from G. lingzhi. We found that 2 could inhibit ROS generation in a dose-dependent manner, inhibit mRNA expression of collagen IV, fibronectin, IL-6 and increase expression of Nrf2 in rat tubular epithelial cells. Furthermore, we found that 2 could reduce urinary albumin levels, abrogate myofibroblastic activation and inhibit the phosphorylation of Smad3 in adriamycin-induced mice. CONCLUSIONS The in vitro and in vivo results suggested that lingzhilactone B could protect against renal injuries by increasing the activities of antioxidants and inhibiting inflammation. The inhibition of Smad3 phosphorylation suggested that this substance displays in vivo antifibrotic activity by a mechanism that is dependent on disruption of Smad3. These results promote understanding of the traditional usage of G. lingzhi and provide promising findings which may be beneficial for anti-kidney disease drug design.

Bioactive compounds from the insect Aspongopus chinensis

Recent studies focusing on unveiling the biological agents of Aspongopus chinensis have led to the identification of four new norepinephrine derivatives (1-4), three new sesquiterpenoids (5-7), and one new lactam (8). In addition, twenty-three known compounds have been identified, most of which were isolated from this insect for the first time. Selected members of insect-derived substances were evaluated for their biological activities against renal protection in high-glucose-induced mesangial cells and COX-2 inhibition.

Two acidic polysaccharides from the flowers of Chrysanthemum morifolium

Two new acidic polysaccharides, F4 and F5, were isolated from the flowers of Chrysanthemum morifolium. Monosaccharide analysis indicated that F4 contained arabinose, galactose and galacturonic acid units in a molar ratio of 1.0:2.3:6.8 and F5 contained arabinose, rhamnose galactose and galacturonic acid units in a molar ratio of 1.0:3.2:1.0:4.3. The results of methylation analysis, partial acid hydrolysis and NMR spectral analysis indicated that F4 had a homogalacturonan main chain with arabinogalactan side chain linked to 3 position of (1 → 3,4)-linked galacturonan and F5 had a rhamnogalacturonan main chain with arabinogalactan side chain linked to 3 position of (1 → 3,4)-linked galacturonan or 4 position of (1 → 2,4)-linked rhamnose. Biological tests revealed that F4 and F5 could simulate the mitogen induced T and B lymphocyte proliferation in vitro.

Two new compounds from Ganoderma lucidum

Two pairs of new enantiomers, lucidulactones A and B (1 and 2), and two known compounds were isolated from Ganoderma lucidum. Their structures were determined by means of spectroscopic methods. The chiral HPLC was used to separate the ( − )- and (+)-antipodes of the new compounds.

Racemic alkaloids from the fungus Ganoderma cochlear

Seven pairs of new alkaloid enantiomers, ganocochlearines C-I (1, 3-8), and three pairs of known alkaloids were isolated from the fruiting bodies of Ganoderma cochlear. The chemical structures of new compounds were elucidated on the basis of 1D and 2D NMR data. The absolute configurations of compounds 1, 3-10 were assigned by ECD calculations. Biological activities of these isolates against renal fibrosis were accessed in rat normal or diseased renal interstitial fibroblast cells. Importantly, the plausible biosynthetic pathway for this class of alkaloids was originally proposed.

Cochlearoids F–K: Phenolic meroterpenoids from the fungus Ganoderma cochlear and their renoprotective activity

Ganoderma mushrooms are of great nutritious and medicinal values. This study was designed to characterize compounds from the fruiting bodies of Ganoderma cochlear and investigate their protective effects against kidney disorders. Six novel meroterpenoids cochlearoids F-K (1-6) were isolated by utilizing phytochemical approaches. Their structures were identified on the basis of extensive spectroscopic data and calculation methods. Biological evaluation shows that compounds 1-4 and 6 exhibit potent inhibitory activity on fibronectin overproduction in TGF-β1-induced HKC-8 cells.

Nonpeptide small molecules from the insect Aspongopus chinensis and their neural stem cell proliferation stimulating properties

Four pairs of enantiomeric hypoxanthine analogues (1, 2, 5 and 6), two pairs of enantiomeric adenine analogues (3 and 4), two pyrazines, aspongpyrazines A (7) and B (8), and a pair of glycerides ((+)-9 and (−)-9), along with twenty-eight known substances were isolated from the insect Aspongopus chinensis. The structures of the new natural products were assigned by using spectroscopic and computational methods. Chiral HPLC was used to separate the (−)- and (+)-antipodes of 1–6, and 9. Several of the new, A. chinensis derived natural products were found to promote proliferation of neural stem cells (NSCs) at a concentration of 10 μM.

Isolation of lingzhifuran A and lingzhilactones D–F from Ganoderma lucidum as specific Smad3 phosphorylation inhibitors and total synthesis of lingzhifuran A

Lingzhifuran A (1) and lingzhilactones D–F (2–4), four new phenolic meroterpenoids were isolated from the fruiting bodies of Ganoderma lucidum. Their structures were identified by spectroscopic data. Chiral HPLC analysis indicates the racemic nature of 2–4. Chiral separation followed by X-ray diffraction analysis discloses the absolute configuration of (−)-2. Compounds 1 and 2 could selectively inhibit TGF-β1-induced Smad3 phosphorylation in rat renal tubular epithelial cells, representing novel scaffolds of selective Smad3 activation inhibitors. Total synthesis accompanied by in vivo rodent experiments reveals antifibrotic activities of 1 against kidney fibrosis. Finally, a plausible biosynthetic pathway for 1 was proposed.