Regioisomers Salviprolin A and B, Unprecedented Rosmarinic Acid Conjugated Dinorditerpenoids from Salvia przewalskii Maxim.

Salvia przewalskii Maxim is a perennial plant from the genus Salvia (family Lamiaceae). The roots of S. przewalskii were long used as a traditional herb to treat blood circulation related illnesses in China. As part of our continuing interest in polycyclic natural products from medicinal plants, two unprecedented adducts comprised of a dinor-diterpenoid and a 9'-nor-rosmarinic acid derivative, linked by a 1,4-benzodioxane motif (1 and 2), were isolated from the roots of S. przewalskii. Their structures were established by extensive spectroscopic approaches including 1D, 2D NMR, and HRFABMS. Their cytotoxic activities against five human tumor cell lines were evaluated.

Bioactive constituents of Salvia przewalskii and the molecular mechanism of its antihypoxia effects determined using quantitative proteomics.

Context: Environmental hypobaric hypoxia induces several physiological or pathological responses in individuals in high-altitude regions. Salvia przewalskii Maxim (Labiatae) (SPM) is a traditional Chinese herbal medicine and has known antibacterial, antiviral, antioxidant, anti-thrombotic, and anti-depressant activities.Objective: This study examined the antihypoxia effects of SPM in vivo.Materials and methods: The dried and pulverised of SPM was extracted from root crude drug with 70% ethanol with ultrasound. Male Sprague-Dawley rats were divided into three groups (n = 10): normal group, hypoxia group (altitude of 4260 m), and hypoxia + SPM group (altitude of 4260 m, SPM of 1.0 g/kg/day). The experiment persisted for 4 weeks. The mean pulmonary arterial pressure (mPAP), hypoxia-inducible factor-1α (HIF-1α) mRNA, and lung pathology were analysed using pulmonary artery pressure recorder, quantitative polymerase chain reaction, and histopathological analysis. Moreover, the effects of SPM on lung proteomes during hypoxia were observed by a TMT-based proteomic approach.Results: Pre-treatment with SPM decreased mPAP (24.86%) and HIF-1α (31.24%), and attenuated the pathological changes in lung tissues. In addition, a total of 28 proteins were differentially expressed in lung of hypoxia + SPM group (fold change > ± 1.2 and p < 0.05). The differentially altered proteins were primarily associated with antioxidative stress, as evidenced by the downregulated expression of Adh7, Cyp2d1, Plod2, Selenow, ND3, and Fabp1, and fructose metabolism, as evidenced by the downregulated expression of Khk and Aldob.Discussion and conclusions: These results suggested that SPM is a promising drug for antihypoxia. The mechanism of action might be related to increasing antioxidant capacity and inhibiting fructose metabolism.

Extract of Salvia przewalskii Repair Tissue Damage in Chronic Hypoxia Maybe through the RhoA-ROCK Signalling Pathway.

Salvia przewalskii Maxim is a traditional Chinese herbal medicine and is known to have antibacterial, antiviral, anti-oxidant, anti-thrombotic and anti-depressant properties. However, the major active components of S. przewalskii and its anti-hypoxic effects are still unclear. This study probed the major active component and anti-hypoxic activity of S. przewalskii. The major active components of S. przewalskii were detected by HPLC. The anti-hypoxic effects of S. przewalskii were detected in mice and a rat model of hypoxic preconditioning. The results showed that there are eight active components, including sodium danshensu, rosmarinic acid, lithospermic acid, salvianolic acid B, dihydrotanshinone I, cryptotanshinone, tanshinone I and tanshinone IIA, and each component showed a certain anti-hypoxic effect. Moreover, S. przewalskii enhanced anti-hypoxia in mice, which was manifested as prolonged survival time in acute hypoxic preconditioning and the amelioration of acute hypoxia-induced changes in the activity of superoxide dismutase (SOD) and lactate dehydrogenase (LDH). In addition, S. przewalskii also repaired tissue damage in chronic hypoxia by downregulating hypoxia inducible factor-1α (HIF-1α), proliferating cell nuclear antigen (PCNA), Bcl-2, CDK4, CyclinD1 and P27Kip1 and inhibiting pro-inflammatory cytokines and the RhoA-Rho-associated protein kinase (ROCK) signalling pathway. Our findings provide new insight into the anti-hypoxic effect of S. przewalskii as a promising agent for high-altitude pulmonary hypertension treatment.

Salvia przewalskii extract of total phenolic acids inhibit TLR4 signaling activation in podocyte injury induced by puromycin aminonucleoside in vitro.

BACKGROUND: TLR4 signaling is known to be involved in podocyte injury. We have previously shown that Salvia przewalskii extract of total phenolic acids (SPE) and its active monomer salvianolic acid B (SalB) and rosmarinic acid (RA) protect podocytes from injury induced by PAN. In the present study, we test whether SPE inhibits TLR4 signaling. METHODS: The conditionally immortalized mouse podocytes were treated with SPE, SalB, RA, SalB + RA or tacrolimus for 30 min, followed by PAN (100 µg/mL) for 24 h. The F-actin staining with phalloidin was used to assess cytoskeletal injury in the podocytes. Western blotting and semi-quantitatives RT-PCR were used to assess the changes of the components in the TLR4 signaling pathway. RESULTS: (1) The F-actin stress fibers of podocytes were almost completely disrupted after PAN treatment for 24 h, and the disruption was significantly alleviated by SPE; (2) the PAN-induced elevation of mRNA levels of TLR4, MyD88 and p65 were inhibited except p65 with high-dose SalB; (3) consistently, the protein levels of TLR4, MyD88 and pp65 were significantly elevated by PAN, and SPE, SalB, RA and admixture, respectively, attenuated the elevations of TLR4 and pp65 proteins; (4) SPE and tacrolimus have a similarly strong effect on inhibition of the expression of TLR4 signaling components. CONCLUSIONS: SPE protects podocytes from PAN-induced injury at least partly through inhibiting TLR4 signaling. SPE is as strong as tacrolimus in inhibiting TLR4 signaling in podocytes.

The effects of Salvia przewalskii total phenolic acid extract on immune complex glomerulonephritis.

CONTEXT: Salvia przewalskii Maxim. (Lamiaceae) is a Chinese herbal medicine that has long been used for the treatment of cardiovascular disease. OBJECTIVE: The study investigated the therapeutic efficacy of S. przewalskii total phenolic acid extract (SPE) on immune complex glomerulonephritis (ICG) in rats. MATERIALS AND METHODS: Sixty-two Wistar rats were randomized into six groups. ICG was induced in all groups except normal control group. SPE was administered intragastrically at 24 h intervals for 40 consecutive days. Urine protein (UP), total serum protein (TSP), serum albumin (SA), serum cholesterol (SC) and serum urea nitrogen (SUN) were measured one day before, on day 20 and 40 after SPE administration. On day 40 after SPE administration, the kidneys were removed and prepared into pathologic sections. In addition, kidney wet mass was measured for calculating the kidney wet mass coefficient (KWMC). RESULTS: UP excretion was reduced significantly on day 20 after SPE administration in all three SPE groups as compared with that in medium group, and this effect was observable continuously until 40 days after SPE administration. Compared with medium group, TSP and SA were increased in all three SPE groups after 40 days treatment, while SC and SUN were decreased. KWMC was decreased significantly in 100 mg/kg SPE group after 40 days treatment compared with that in medium group. Histopathologic analyses showed that renal inflammatory infiltration and kidney intumesce were alleviated in all three SPE groups. CONCLUSIONS: SPE may be a potential therapeutic drug for glomerulonephritis.

Salviprzols A and B, C21- and C22-terpenoids from the roots of Salvia przewalskii Maxim.

Two C21- and C22-terpenoids, salviprzols A (1) and B (2), together with 24 known compounds including 17 diterpenoids (3-19), a triterpenoid (20), and 6 phenolic derivatives (21-26), were isolated from the roots of Salvia przewalskii Maxim. Salviprzols A and B represented a new subtype of C23-terpenoids featured by an additional 2-oxopropyl moiety at C-12 and a rare γ-hydroxyl-α-methyl-α,ß-unsaturated-γ-lactone ring system. Their structures were elucidated by extensive spectroscopic analyses, and the structure of 2 was confirmed by a single-crystal X-ray diffraction crystallography. The cytotoxic activities of the new isolates were tested. A plausible biosynthetic pathway for 1 and 2 was also proposed.