Salvia miltiorrhiza (S. miltiorrhiza) represents a crucial component of traditional Chinese medicine, demonstrating effects on blood circulation activation and stasis removal, and has been widely utilized in asthma treatment. This study isolated a novel phenolic acid (S1) from S. miltiorrhiza and investigated its anti-asthmatic activity and underlying mechanisms for the first time. An allergic asthma (AA) model was established using ovalbumin (OVA). The mechanism of S1's effects on AA was investigated using multi-factor joint analysis, flow cytometry, and co-culture systems to facilitate clinical asthma treatment. S1 (10 or 20 mg·kg-1) was administered daily to mice with OVA-induced AA (OVA-AA) during days 21-25. The study examined airway responsiveness, lung damage, inflammation, and levels of immunoglobulin E (IgE), PGD2, interleukins (IL-4, 5, 10, 13, 17A), tumor necrosis factor α (TNF-α), GM-CSF, CXCL1, CCL11, and mMCP-1. Additionally, mast cell (MC) activation and degranulation were explored, along with T helper type 17 (Th17)/Treg immune cells and TLR4 pathway biomarkers. The antagonistic activity of that specific antagonist of TLR4 (TAK-242) (1 µmol·L-1), a specific TLR4 blocker, against S1 (10 µmol·L-1) was examined in co-cultured 16HBE cells and bone marrow-derived cells (BMDCs) or splenic lymphocytes (SLs) induced with LPS (1 µg·mL-1) to elucidate the TLR4 pathway's mediating role. S1 demonstrated reduced airway responsiveness, lung damage, and inflammation, with downregulation of IgE, PGD2, interleukins, TNF-α, GM-CSF, CXCL1, CCL11, and mMCP-1. It also impeded MC activation and degranulation, upregulated IL-10, and influenced Th17/Treg immune cell transformation following OVA challenge. Furthermore, S1 inhibited the TLR4 pathway in OVA-AA mice, and TLR4 antagonism enhanced S1's positive effects. Analysis using an OVA-AA mouse model demonstrated that S1 alleviates AA clinical symptoms, restores lung function, and inhibits airway response. S1's therapeutic effects occur through regulation of Th17/Treg immune cells and inflammation, attributable at least partially to the TLR4 pathway. This study provides molecular justification for S1 in AA treatment.
Six undescribed compounds (1-6) and twenty-three known analogues (7-29) were isolated from the fresh roots of Rehmannia glutinosa. The structures of the compounds (1-29) were established through the application of spectroscopic analysis. Compounds 3, 4, 6, 8, 13, 18, 21, 22, 25, and 28 exhibited excellent anti-pulmonary fibrosis activity. The potential mechanistic pathway of 3 was also investigated, whose results indicate that compound 3 ameliorate TGF-(31 induced BEAS-2B cell injury via PI3K/AKT/NF-kappa B signaling pathway.
Background: Salvia miltiorrhiza Bunge (Labiatae) (DS) is a key part of the traditional Chinese medicine, whose roots are used to remove blood stasis, relieve pain, eliminate carbuncle and calm the nerves. Our research team found that the DS extract could significantly reverse LPS-induced lung injury, and five new diterpenoid quinones in DS extract with excellent lung protective activity for the first time. However, the material basis and mechanism of DS on pulmonary fibrosis (PF) needs to be explored in depth. Objective: Bleomycin (BLM) was employed to establish the PF model, and Transcriptome and Surface plasmon resonance (SPR) ligand fishing technology were used to explore the material basis and mechanism of DS on PF, and provided theoretical research for clinical treatment of PF. Methods: DS extract (24.58 or 49.16 mg/kg, i.g.) was administered daily from Day 8 to Day 28, followed by intratracheal BLM drip (5 mg/kg) to induce PF. Data about the influences of DS on PF were collected by transcriptome sequencing technology. Pulmonary ultrasound, airway responsiveness, lung damage, collagen deposition, and the levels of TNF-alpha, IL -1f, apoptosis, oxidative stress (OS), immune cells, TGF-f1, alpha-SMA, E-Cadherin and Collage I were examined. The affinity component (Przewalskin) in DS extract targeted by TGF-f1 was fished by SPR ligand fishing technology. Furthermore, an in vivo PF mouse model and an in vitro TGF-f1 induced BEAS2B cell model were established, to explore the mechanism of Przewalskin on PF from the apoptosis, OS and epithelial mesenchymal transformation pathway. Results: DS extract improved pulmonary ultrasound, reduced lung damage and collagen deposition, downregulated TNF-alpha, IL -1f, apoptosis, OS, TGF-f1, alpha-SMA, E-Cadherin and Collage I, transformed immune cells following Bleomycin challenge. Furthermore, affinity component (Przewalskin) also improved pulmonary ultrasound and airway responsiveness, reduced lung damage and collagen deposition, downregulated TNF-alpha, IL -1f, apoptosis, OS in vivo and in vitro. Conclusion: Analysis using a mouse model revealed that DS extract and Przewalskin can relieve clinical symptoms of PF, reduce lung injury and improve lung function. Meanwhile, DS extract and Przewalskin can improve BLMinduced PF by inhibition of, OS, apoptosis and collagen deposition might via the TGF-beta 1 pathway. This study provides references to identification of novel therapeutic targets, thereby facilitating drug development for PF.
Two new undescribed compounds, jiofuran acid A (1) and 8′-hydroxyl episesaminone (2), together with seven known compounds (3–9) were isolated from the fresh roots of Zhongsheng No.1 Rehmannia glutinosa. Their structures were established by spectroscopic techniques (HR-ESI-MS, 1D NMR, 2D NMR), and absolute configurations were resolved by comparing their experimental and calculated ECD spectra. Bioassay results demonstrated compounds 1–3 exhibited the obvious anti-pulmonary fibrosis activity.
Six new compounds, (7R,8S,8′R)-balanophorone (1), (7′S,8′R,8R)-yunnanensin A (2), (3S)-thunberginol C (3), (8R,8′R)-maninsigin B (4), (7S,8R)-4,7,8-dihydroxy-9,9-dimethyl-chroman (5), and 4-hydroxy-1-(4-hydroxy-3-methoxyphenyl)butan-1-one (6), along with eight known compounds (7–14), were isolated from the herbaceous stems of Ephedra intermedia Schrenket C. A. Meyer. Their structures were elucidated based on their spectroscopic (MS, NMR, IR, and UV) data, and their absolute configurations were determined by comparing their calculated and experimental electronic circular dichroic (ECD) spectra. Moreover, compounds 1 and 3–6 were evaluated for their ability to protect human pulmonary epithelial cells (BEAS-2B) from injury induced by lipopolysaccharide (LPS) in vitro. The results showed that compound 6 exhibited a significant protective effect against LPS-induced injury in BEAS-2B, and compound 5 exhibited a slightly protective effect at the concentration of 10 μM.
Fifteen undescribed diterpenoid quinones salviamilthone A-O (1-15), together with three known diterpenoid quinones (16-18), were isolated from the roots of Salvia miltiorrhiza Bunge. Their structures were elucidated using 1D and 2D NMR data, while the relative and absolute configurations were confirmed by NOESY correlations and comparison between experimental and calculated ECD spectra. In the evaluation of bioactivities, salviamilthone J (10), salviamone (18) (10 mu M) significantly increased cell viability and decreased the expression of IL-1 beta in lipopolysaccharide-induced BEAS-2B cells. These data provide the molecular justification for the usage of Salvia miltiorrhiza in treating acute lung injury.
Seven new diterpenoids quinones (1-6), together with five known ones (7-11), were isolated from the roots of Salvia miltiorrhiza Bunge. Their structures were elucidated by using 1D and 2D NMR data, while the relative and absolute configurations were confirmed by interpretations of the NOESY correlations and comparison of the experimental and calculated ECD spectra. In the evaluation of bioactivities, salviamilthiza C (3), significantly increased cell viability and decreased the expression of IL-1β in LPS-induced BEAS-2B cells.
Two new monoterpenoids, muhuang acid A (1) and muhuang acid B (2), together with six known compounds (3-8) were isolated from the stems of Ephedra sinica Stapf. Their structures were assigned by 1D and 2D NMR data, and absolute configurations were resolved by comparing their experimental and calculated ECD spectra. All isolates were evaluated for their protective effects on N9 cells injury induced by LPS. The results showed that compounds 7 and 8 exhibited moderate anti-inflammatory activity, with the EC50 values of 22.7 and 15.0 mu M, respectively.
Three pairs of undescribed diarylpentanoid enantiomers (1-3) and five undescribed phenylpropanoids (4-8), along with seven known compounds, were isolated from the roots of Anthriscus sylvestris. The structures of compounds (1-8) were determined by analysis of their 1D and 2D NMR spectra, HRESIMS, and electronic circular dichroism. In addition, the inhibitory activities against hypoxia-stimulated pulmonary arterial smooth muscle cells abnormal proliferation were evaluated by MTT assay. The mRNA expression levels of Bcl-2, BAX, Caspase3, and IL-6 were detected by quantitative real-time PCR. The results showed that compounds (-)-1, (+)-1, (-)-2, (+)-3, 4, 8-10, 14, and 15 inhibited the abnormal proliferation of PASMCs by regulating the levels of apoptosis and inflammatory factors.
A new flavonoid, saffloflavone , along with six known compounds, kaempferol-3-O-rutinoside, kaempferol-3-O-sophoroside, quercetin-3-O-β-d-glucoside, quercetin-7-O-β-d-glucoside, luteolin-7-O-β-d-glucoside and kaempferol 3-O-β-d-glucoside were isolated from the flowers of Carthamus tinctorius L. All the structures were determined by interpretation of their spectroscopic data. The cardioprotective effects of all the isolates against oxidative stress of H9c2 cells induced by H2O2 were investigated. The results showed that compounds 4-6 exhibited protective effects against of H9c2 cells injury induced by H2O2.
Background: Severe inflammation of the lungs results from acute lung injury (ALI), a common life-threatening lung disease with a high mortality rate. The ligand-activated transcription factor peroxisome proliferator-activated receptor (PPAR) gamma plays essential roles in diverse biological processes including inflammation, meta-bolism, development, and immune response. Salvianolactone acid A (SA) is a terpenoid derived from the herb Salvia miltiorrhiza. However, there is a scarcity of experimental evidence indicating whether the effect of SA on ALI occurs via PPAR-gamma. Methods: SA (20 or 40 mg/kg, i.g., 1 time/day) was administered to mice for 3 d, followed by the induction of ALI by intranasal lipopolysaccharide (LPS, 10 mg/kg). The lung function and levels of inflammation, reactive oxygen species (ROS), immune cells, apoptosis, and PPAR-gamma were examined. The antagonistic activity of GW9662 (GW, 1 mu M, specific PPAR-gamma blocker) and PPAR-gamma transfection silencing against SA (10 mu M) in BEAS-2B cells induced by LPS (10 mu g/ml, 24 h) was also investigated to assess whether the observed effects caused by SA were mediated by PPAR-gamma. Results: The results showed that lung histopathological injury, the B-line, the fluorescence intensity of live small animal, and the biomarkers in BALF or lung in the treatment of SA could regulate significantly. In addition, SA obviously decreased the levels of ROS and apoptosis in the primary lung cells, and MDA, increased the levels of GSH-Px and SOD. SA reduced levels of macrophages and neutrophils. Furthermore, SA reduced the protein levels of Keap-1, Cleaved-caspase-3, Cleaved-caspase-9, p-p65/p65, NLRP3, IL-1 beta, and upregulated the levels of p-Nrf2/Nrf2, HO-1, Bcl-2/Bax, PPAR-gamma, p-AMPK/AMPK in lung tissue. In addition, silencing and inhibition of PPAR-gamma effectively decreased the protective effects of SA in BEAS-2B cells induced by LPS, which might indicate that the active molecules of SA regulate ALI via mediation by PPAR-gamma, which exhibited that the effect of SA related to PPAR-gamma. Conclusions: The anti-ALI effects of SA were partially mediated through PPAR-gamma signaling. These data provide the molecular justification for the usage of SA in treating ALI and can assist in increasing the comprehensive utili-zation rate of Salvia miltiorrhiza.
目的 研究薯蓣(Dioscorea opposite Thunb.)叶腋间珠芽(零余子)的化学成分.方法 采用硅胶、Toyopearl HW-40C、Sephadex LH-20、MCI gel CHP-20 及 ODS等柱色谱技术结合半制备液相色谱进行分离纯化,根据其理化性质、核磁共振(NMR)谱、质谱鉴定所得化合物结构.结果 从零余子中分离得到16个化合物,分别鉴定为吐叶醇(1)、长寿花糖苷(2)、苯乙醇-8-0-β-D-葡萄糖苷(3)、artselaeroside A(4)、benzyl-O-β-D-apiofuranosyl-(1 →2)-β-D-glucopyranoside(5)、seguinoside E(6)、di-oscorolide A(7)、芹菜素(8)、5,7-dihydroxy-2-[2-(4-hydroxyphenyl)ethyl]chromone(9)、2,7-dihydroxy-4,6-dimethoxyphenanthrene(10)、对羟基苯乙酮(11)、2-hydroxy-3,5,7-trimethoxy-9,10-dihydrophenanthrene(12)、杜鹃醇(13)、3-甲氧基-4-羟基-苯乙醇(14)、3,5-二甲氧基-4-羟基-苯乙醇(15)、4-(3,4-二羟基苯基)-2-丁酮(16).结论 化合物2~6、9、11~16为首次从薯蓣属中分离得到,其他化合物为首次从薯蓣中分离得到.
Nine undescribed compounds, together with 21 known components, were isolated from the fresh roots of Rehmannia glutinosa. Their structures were elucidated based on spectroscopic data analysis, and the absolute configurations of undescribed compounds were determined by comparison of their calculated and experimental electronic circular dichroic (ECD) spectra and interpretation of their optical rotation data. The α-glucosidase inhibitory effects of the isolated compounds were investigated and all of them exhibited slightly inhibitory activities.
Two new lignans, eplignans B and C (1 and 2), along with seven known compounds (3-9) were isolated from the herbaceous stems of Ephedra intermedia. Their structures were elucidated based on their spectroscopic data. The absolute configurations of 1 and 2 were determined by comparing their calculated and experimental electronism circular dichroic (ECD) spectra. Moreover, all compounds (1-9) were evaluated for their a-glucosidase inhibitory effects and exhibited mild inhibitory activities with the IC50 values greater than 50 mu M.
A new lignan eplignan A (1), along with six konwn lignans (2-7) was isolated from the herbaceous stems of Ephedra intermedia Schrenket C. A. Meyer. Their structures were elucidated based on the spectroscopic evidence, mainly including NMR and HRESIMS data. The absolute configuration of 1 was determined by comparing calculated and experimental electronic circular dichroic (ECD) spectra. Moreover, all compounds (1-7) were evaluated for their protective effects against the BEAS-2B cells injury induced by TGF-beta 1 in vitro, and the results showed that compounds 1, 2, 4, and 6 exhibited significantly protective activities at the concentration of 10 mu M.
A new amide, named rehmagluamide (1), and a new hydroxycinnamic acid derivative, named nepetoidin F (2), together with six known compounds, 2'-O-methyluridine (3), puroglutamic acid (4), biliverdic acid (5), peterolactam (6), nicotinic acid (7), nicotinamide (8), were isolated from the fresh roots of Rehmannia glutinosa. All the structures of compounds were identified by the interpretation of their spectroscopic data and comparison with those reported in the literatures. The protective effects of compounds 1-7 on normal rat kidney tubule epithelioid (NRK-52e) cells injury induced by LPS were investigated. The results indicated that compounds 1, 2, and 7 exhibited protective effects against LPS-induced NRK 52e cells injury.
Acute lung injury (ALI) is a common critical disease with a high mortality rate. Natural products have marked efficacy in the prevention and treatment of ALI, in addition, estrogen and its receptors are involved in the pathogenesis and development of lung injury. Our previous research shows that sesquiterpenes isolated from the stems and leaves of Dioscorea opposita Thunb. have anti-inflammatory and estrogenic-like activity. In the present study, sesquiterpene (A1) is a natural extract from the stems and leaves of Dioscorea opposita Thunb. with a view to determining whether A1 can improve lung function in a mouse model of LPS-induced ALI and exploring the involvement of the estrogen receptor β (ERβ) pathway. A1 (20 or 40 mg/kg, i. g., 2 times/day) was administered for 3 d, followed by the induction of ALI via an intratracheal LPS drip (5 mg/kg/2 h). The lung function and levels of inflammation, immune cells, apoptosis, and ERβ expression were examined. The antagonistic activity of specific ERβ blocker (THC, 1 μM) against A1 (20 μM) in co-cultured BEAS-2B cells and splenic lymphocytes induced with LPS (1 μg/mL, 24 h) was also investigated to assess whether the observed effects of A1 were mediated by ERβ. A1 improved lung function, regulated the immune system, and decreased inflammation and apoptosis. Moreover, A1 increased the expression of ERβ in LPS-induced mice, and antagonism of ERβ decreased the protective effects of A1 in a co-culture system. A1 had anti-ALI effects that might partially mediated through ERβ signaling. Our data provide molecular justification for the use of A1 in the treatment of ALI.
This study aimed to report the structure elucidation of the compounds isolated from Salvia miltiorrhiza, and their biological evaluations. Ten undescribed diterpenoid quinones and 10 known analogues were isolated from the dried roots of S. miltiorrhiza. Their structures were elucidated by extensive analysis, including nuclear magnetic resonance, high-resolution mass spectra, and ultraviolet and infrared spectra. Their absolute configurations were determined by comparing the experimental and calculated electronic circular dichroism spectra. In the evaluation of bioactivities, Salvianolactone acid I, epi-danshenspiroketallactone F, danshinspiroketallactone, grandifolia G, and 2H-Naphtho [1,8-bc]furan (10 μM) significantly increased cell viability and decreased the nuclear transport of p-P65 in lipopolysaccharide-induced bronchial epithelial cells. It was concluded that the diterpenoid quinones might belong to potent targeted lung-protective agents.
A new eremophilanolide, serratifolide F (1), and six known compounds were isolated from the fresh roots of Rehmannia glutinosa. Their structures were characterized by analysis of NMR, CD, HRESIMS, and comparison of the data in previous literatures. The protective effects against lipopolysaccharide (LPS)-stimulated damage on normal rat kidney tubule epithelioid (NRK-52e) cells of the compounds were evaluated using MTT assay and real time cellular analysis (RTCA). The results showed that compound 3 exhibited renoprotective activity with EC50 value of 45.1 μM.