Fan-Fan Hou

Acortatarins A and B, two novel antioxidative spiroalkaloids with a naturally unusual morpholine motif from Acorus tatarinowii.

Acortatarins A (1) and B (2), two novel spiroalkaloids with a naturally unusual morpholine motif, were isolated from the rhizome of Acorus tatarinowii. Their structures with absolute configuration were determined by spectroscopic methods, X-ray diffraction analysis, and Moshers method. Importantly, compound 1 could significantly inhibit reactive oxygen species production in high-glucose-stimulated mesangial cells in a dose- and time-dependent manner.

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.

Isolation and Identification of Compounds Responsible for Antioxidant Capacity of Euryale ferox Seeds

Euryale ferox seed is consumed medicinally or for food in China. The present study revealed it to contain significant antioxidant activity, which may be associated with its medical applications as a proteinuria inhibitor of diabetic nephropathy. This study resulted in the identification of 3 new sesquineolignans, named euryalins A-C (1-3), and 16 known compounds, which were all first isolated from this plant apart from 5,7,4-trihydroxy-flavanone. The antioxidant potential of the partial isolates was evaluated using the DPPH radical scavenging assay and mesangial cellular assay. Compounds 2, rel-(2α,3β)-7-O-methylcedrusin (4), syringylglycerol-8-O-4-(sinapyl alcohol) ether (5), and (+)-syringaresinol (7) were found to be most active on DPPH assay, whereas compounds 2, 4, 7, (1R,2R,5R,6S)-2-(3,4-dimethoxyphenyl)-6-(3,4-dihydroxyphenyl)-3,7-dioxabicyclo[3.3.0]octane, and buddlenol E could significantly inhibit high glucose-stimulated reactive oxygen species production in mesangial cells. The results suggested that E. ferox seed could be considered as an excellent source of natural antioxidants and is useful in the prevention of diabetic nephropathy.

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 Aerial Parts of Brachystemma calycinum and Structural Revision of an Octacyclopeptide

Four new cyclic peptides, brachystemins F-I (1-4), and 11 known compounds were isolated from the aerial parts of Brachystemma calycinum. The absolute configurations of compounds 1-4 were assigned using Marfeys method. The structure of compound 5 was revised from cyclo(Pro¹-Phe²-Leu³-Ala⁴-Thr⁵-Pro⁶-Ala⁷-Gly⁸) to cyclo(Pro¹-Pro²-Ala³-Gly⁴-Leu⁵-Ala⁶-Thr⁷-Phe⁸) with QTOF/MS and X-ray diffraction analysis. The N-containing compounds were assessed for their inhibitory effects on the secretion of monocyte chemokine ligand 2 (CCL-2), interleukin 6 (IL-6), and collagen IV against high-glucose-stimulated mesangial cells. Compound 5 was evaluated for its effects on collagen I, reactive oxygen species (ROS), superoxide anion (O₂(•⁻)) production, and cell viability in mesangial cells, and on nitric oxide (NO) production in macrophage cells.

Diabetic nephropathy-related active cyclic peptides from the roots of Brachystemma calycinum.

Three new cyclic peptides, namely duanbanhuains A-C (1-3), were isolated from the roots of Brachystemma calycinum which is a traditional medicine used to treat rheumatic diseases. Their structures were identified by means of a suite of MS and NMR experiments. These compounds were purposely evaluated for their inhibitory effects on the release of MCP-1, IL-6, collagen IV and reactive oxygen species (ROS) against high-glucose-stimulated mesangial cells. The results showed that compounds 1 and 2 exhibited potent inhibition on the production of IL-6, collagen IV and ROS at the 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.

Belamchinanes A–D from Belamcanda chinensis: Triterpenoids with an Unprecedented Carbon Skeleton and Their Activity against Age-Related Renal Fibrosis

Belamchinanes A-D (1-4), four triterpenoids with an unprecedented skeleton, were isolated from the seeds of Belamcanda chinensis and fully characterized. The structures of belamchinanes feature a 4/6/6/6/5 polycyclic system in which a four-membered carbocyclic ring bridges the C-1 and C-11 positions of a classical triterpenoid framework. A plausible pathway for the biosynthesis of 1-4 is proposed. Biological studies reveal that 1-4 dose-dependently protect age-related renal fibrosis in vitro .