Unraveling the Therapeutic Mechanism of Saussurea involucrata against Rheumatoid Arthritis: A Network Pharmacology and Molecular Modeling-Based Investigation.

Rheumatoid arthritis (RA) is a chronic autoimmune disease with a global prevalence of approximately 0.46%, causing significant impairments in patients' quality of life and an economic burden. Saussurea involucrata (SI) has long been used in traditional medicine to treat RA, but its underlying mechanism remains unclear. This study utilized network pharmacology and molecular docking to explore the potential pharmacological effects of bioactive compounds in SI on RA. A total of 27 active compounds were identified, along with 665 corresponding targets. Additionally, 593 disease-related targets were obtained from multiple databases, with 119 common targets shared with SI. The high-ranking targets mainly belong to the MAPK family and NF-κB pathway, including MAPK14, MAPK1, RELA, TNF, and MAPK8, all of which are associated with inflammation and joint destruction in RA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed significant pathways related to IL-17 signaling, Th17 cell differentiation, and osteoclast differentiation. Molecular docking and dynamic simulations demonstrated strong interactions between several flavonoids and RA-related targets. Xuelianlactone, Involucratin, and Flazin exhibit outstanding binding efficacy with targets such as MAPK1, MAPK8, and TNF. These findings provide valuable insights into the therapeutic potential of SI for RA and offer directions for further drug development.

RD29A promoter constitutively drives a rice Hd3a expression to promote early-flowering in Saussurea involucrate Kar. et Kir. ex Maxim.

S. involucratae, an endemic and endangered plant, is a valuable and traditional Chinese medicinal herb. In order to control the flowering time of S. involucratae, we used the well-known stress inducible RD29A promoter to drive Hd3a (a FT ortholog from rice) expression in S. involucratae. Unexpectedly, the majority of regenerated buds in RD29A::Hd3a transgenic lines (S-RH) produced flowers in tissue culture stage under normal growth (25 ± 2 °C) condition. Their flowering time was not further influenced by salt treatment. Hd3a in S-RH was strongly expressed in MS media supplemented with or without 50 mM NaCl. RD29A::GUS transgenic experiments further revealed that RD29A constitutively promoted GUS expression in both S. involucrate and halophyte Thellungiella halophile, in contrast to glycophic plants Oryza sativa L. 'Zhonghua 11', in which its expression was up-regulated by cold, salinity, and drought stress. The results supported the hypothesis that RD29A promoter activity is inducible in stress-sensitive plants, but constitutive in stress-tolerant ones. Importantly, S-RH plants produced pollen grains and seeds under normal conditions. Additionally, we found that OsLEA3-1::Hd3a and HSP18.2::Hd3a could not promote S. involucrate to flower under either normal conditions or abiotic stresses. Taken together, we demonstrated the potential of RD29A::Hd3a might be served as a feasible approach in breeding S. involucrate under normal condition.

Saussurea involucrata oral liquid regulates gut microbiota and serum metabolism during alleviation of collagen-induced arthritis in rats.

Saussurea involucrata oral liquid (SIOL) can clinically relieve symptoms, such as joint pain and swelling, and morning stiffness, in patients with rheumatoid arthritis (RA). However, the mechanism of action remains unclear. This study used a combination of gut microbiota and serum metabolomics analysis to investigate the effects and potential mechanisms of SIOL intervention on rats with RA induced by type II bovine collagen and Freund's complete adjuvant. Results showed that SIOL treatment consequently improved the degree of ankle joint swelling, joint histopathological changes, joint pathological score, and expression of serum-related inflammatory cytokines (interleukin (IL)-1ß, IL-4, IL-6, IL-10, and tumor necrosis factor-α) in RA model rats. 16 S rRNA sequencing results showed that SIOL increased the relative richness of the Lactobacillus and Bacteroides genus and decreased the relative richness of Romboutsia, Alloprevotella, Blautia, and Helicobacter genus. Serum nontargeted metabolomic results indicated that SIOL could regulate metabolites related to metabolic pathways, such as glycine, serine, threonine, galactose, cysteine, and methionine metabolism. Spearman correlation analysis showed that the regulatory effects of SIOL on the tricarboxylic acid (TCA) cycle, phenylalanine metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis, and glyoxylate and dicarboxylate metabolism pathways were correlated with changes in the richness of the Lactobacillus, Romboutsia, Bacteroides, and Alloprevotella genus in the gut microbiome. In conclusion, this study revealed the ameliorative effects of SIOL on RA and suggested that the therapeutic effects of SIOL on RA may be related to the regulation of the community richness of the Lactobacillus, Romboutsia, Bacteroides, and Alloprevotella genus, thereby improving the TCA cycle; phenylalanine metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis, and glyoxylate and dicarboxylate metabolism-related pathways.

Comparison of Differences in Chemical Composition and Related Antioxidant Activity of Snow Lotus from Different Origins.

The snow lotus is an endangered traditional Chinese medicinal herb. Saussurea involucrata, Saussurea laniceps, and Saussurea medusa, the three main snow lotus species (five herbs and two S. involucrata cell cultures), were selected for this study. Snow lotus (XLs) was extracted using 75 % (v/v) ethanol. Two reversed phase-high performance liquid chromatography-diode array detector methods were developed and validated for the determination of 10 representative components in XLs. The antioxidant efficacy of XLs and their components was investigated using DPPH, ABTS free radical scavenging, and ROS inhibition experiments. The results showed that the IC50 for DPPH scavenging ranged from 0.06-0.29 mg/mL for XLs and from 0.13-0.63 mg/mL for ABTS, and could downregulate ROS to varying degrees. The results of the antioxidant activity showed that rutin, quercetin, and isochlorogenic acid A contributed to the antioxidant capacity of XLs. The high content and activity of the cell cultures indicate that they can serve as an effective alternative to snow lotus, thus providing a theoretical basis for the selection of herbs and cell cultures to fulfil various needs.

Anti-Melanogenesis Effect of Polysaccharide from Saussurea involucrata on Forskolin-Induced Melanogenesis in B16F10 Melanoma Cells.

As one of the prominent medicinal plants listed in the Chinese pharmacopoeia (2020), Saussurea involucrata (Kar. et Kir.) Sch.-Bip was demonstrated to possess various therapeutic effects. In our recent research, we extracted the polysaccharides from S. involucrata (SIP) at optimal conditions and conducted further structure elucidation on the main fraction as well as the confirmation of its possible anti-inflammatory activity. Hence, in this work, we assessed the in vitro antioxidant activity and anti-melanogenesis effects of the crude SIP in forskolin-induced B16F10 melanoma cells. The results show that SIP possessed strong antioxidant activity and was effective in concentration-dependently decreasing melanin formation and inhibiting tyrosinase activity in forskolin-induced B16F10 cells. Based on these results, the inhibitory mechanism of melanogenesis was investigated by measuring Tyrosinase (TYR), Tyrosinase related protein-1 (TRP-1), Tyrosinase related protein-2 (TRP-2), Microphthalmia-associated transcription factor (MITF), cAMP-response element binding protein (CREB), mitogen-activated protein kinases (MAPK) signaling protein members, and ß-catenin degradation in forskolin-induced B16F10 cells. The anti-melanogenesis response of SIP might be attributed to the regulation of c-Jun N-terminal kinase (JNK) phosphorylation and ß-catenin degradation pathways. These results suggest that polysaccharides from S. involucrata possess a strong anti-melanogenic effect, and thus could be used as a high-value natural material for skin whitening in cosmeceutical industries.

Integrated metabolism, network pharmacology, and pharmacokinetics to explore the exposure differences of the pharmacodynamic material basis in vivo caused by different extraction methods for Saussurea involucrata.

ETHNOPHARMACOLOGICAL RELEVANCE: Saussurea involucrata Kar.et Kir. (S.I.) has long been used as a precious national medicine and clinically proven to be an effective treatment for rheumatoid arthritis (RA) and cardiovascular diseases. In clinical practice, two extraction methods of S.I., including water decoction and alcohol extraction, are prescribed to treat the same conditions. Nevertheless, no study has been performed on the exposure differences of the pharmacodynamic material basis in vivo caused by different extraction methods. AIM OF THE STUDY: Based on the integrated strategy of metabolism, network pharmacology, and pharmacokinetics, we aimed to reveal exposure differences in pharmacodynamic substances caused by different extraction methods. MATERIALS AND METHODS: Ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS) was employed to identify the chemical constituents of S.I. extracts and the metabolites in vivo after administration. Based on the analysis of prototype components in vivo, the major exposure active constituents, potential therapeutic targets and possible pharmacological mechanisms in RA treatment were investigated using network pharmacological analysis. Seven critical active components, including quercetin, hispidulin, apigenin, chlorogenic acid, arctigenin, syringin, and umbelliferone, were quantitatively compared between the alcohol, and aqueous extraction methods, which had been confirmed by the reference substance. RESULTS: The chemical comparison demonstrated that the types of chemicals in the two extracts were identical, mainly flavonoids, phenylpropanoids, coumarins, lignins, sesquiterpene lactones, and others, but the contents of the primary constituents in the aqueous extract were lower than those of the alcohol extract. A total of 30 prototype components and 174 metabolites were analyzed and identified in rat plasma, urine, fecal, and bile samples. Twenty-three prototype components were analyzed by network pharmacology, and seven critical active components were selected as representative markers for the pharmacokinetic study. Pharmacokinetic studies had shown that the Tmax values of apigenin, hispidulin, chlorogenic acid, arctigenin, and syringin after the oral administration of the alcohol extract were lower than those after the oral administration of the aqueous extract, and the above components in the alcohol extract could increase the absorption. Compared with the aqueous extract group, the Tmax and T1/2 of quercetin and umbelliferone were longer; it was suggested that alcohol extraction might have a slow-release and long-term effect on these two components. The relative bioavailability of apigenin, hispidulin, quercetin, chlorogenic acid, and umbelliferone in the alcohol extract group were higher than those in the aqueous extract group, which was consistent with the traditional clinical experience that alcohol extract could improve the efficacy of S.I. CONCLUSIONS: The major exposure active constituents in vivo were screened. The representative components that could be used in pharmacokinetics were determined by integrating network pharmacology and metabolism studies. The critical active compounds were quantitatively compared between the alcohol and aqueous extraction methods. This study clarified that flavonoids, coumarin, and phenylpropanoids might be the primary material basis that caused the exposure differences between aqueous and alcoholic extracts from S.I.. This research aimed to provide the basis of metabolism in vivo for further studying these pharmacodynamic differences.

Exploring the possible molecular targeting mechanism of Saussurea involucrata in the treatment of COVID-19 based on bioinformatics and network pharmacology.

OBJECTIVE: Based on bioinformatics and network pharmacology, the treatment of Saussurea involucrata (SAIN) on novel coronavirus (COVID-19) was evaluated by the GEO clinical sample gene difference analysis, compound-target molecular docking, and molecular dynamics simulation. role in the discovery of new targets for the prevention or treatment of COVID-19, to better serve the discovery and clinical application of new drugs. MATERIALS AND METHODS: Taking the Traditional Chinese Medicine System Pharmacology Database (TCMSP) as the starting point for the preliminary selection of compounds and targets, we used tools such as Cytoscape 3.8.0, TBtools 1.098, AutoDock vina, R 4.0.2, PyMol, and GROMACS to analyze the compounds of SAIN and targets were initially screened. To further screen the active ingredients and targets, we carried out genetic difference analysis (n = 72) through clinical samples of COVID-19 derived from GEO and carried out biological process (BP) analysis on these screened targets (P ≤ 0.05)., gene = 9), KEGG pathway analysis (FDR≤0.05, gene = 9), protein interaction network (PPI) analysis (gene = 9), and compounds-target-pathway network analysis (gene = 9), to obtain the target Point-regulated biological processes, disease pathways, and compounds-target-pathway relationships. Through the precise molecular docking between the compounds and the targets, we further screened SAIN's active ingredients (Affinity ≤ -7.2 kcal/mol) targets and visualized the data. After that, we performed molecular dynamics simulations and consulted a large number of related Validation of the results in the literature. RESULTS: Through the screening, analysis, and verification of the data, it was finally confirmed that there are five main active ingredients in SAIN, which are Quercitrin, Rutin, Caffeic acid, Jaceosidin, and Beta-sitosterol, and mainly act on five targets. These targets mainly regulate Tuberculosis, TNF signaling pathway, Alzheimer's disease, Pertussis, Toll-like receptor signaling pathway, Influenza A, Non-alcoholic fatty liver disease (NAFLD), Neuroactive ligand-receptor interaction, Complement and coagulation cascades, Fructose and mannose metabolism, and Metabolic pathways, play a role in preventing or treating COVID-19. Molecular dynamics simulation results show that the four active ingredients of SAIN, Quercitrin, Rutin, Caffeic acid, and Jaceosidin, act on the four target proteins of COVID-19, AKR1B1, C5AR1, GSK3B, and IL1B to form complexes that can be very stable in the human environment. Tertiary structure exists. CONCLUSION: Our study successfully explained the effective mechanism of SAIN in improving COVID-19, and at the same time predicted the potential targets of SAIN in the treatment of COVID-19, AKR1B1, IL1B, and GSK3B. It provides a new basis and provides great support for subsequent research on COVID-19.

Chemical constituents from the aerial parts of Saussurea involucrata with their inhibitory activities on α-glucosidase.

A new aurone glycoside named licoagroaurone 6-O-α-ʟ-arabinopyranoside (1), together with six known compounds (2-7), was isolated from EtOAc-soluble extract of the aerial parts of Saussurea involucrata. Their structures were elucidated on the basis of spectroscopic methods. All compounds were evaluated for their inhibitory activities against α-glucosidase in vitro. Among them, compounds 1 and 6 showed significant inhibitory activities on α-glucosidase with the IC50 values of 47.1 and 57.7 µM, respectively.

[Research progress on culture technologies,chemical components,and pharmacological activities of Saussurea involucrata cells].

Saussurea involucrata,a traditional Chinese medicinal material,is effective in the treatment of rheumatoid arthritis with cold-dampness blockage syndrome,cold pain in lower abdomen,and menstrual irregularities. However,due to the specific habitat,low natural reproduction rate,slow growth,and overexploitation,it is at the high risk of extinction. S. involucrata cells can be obtained through callus culture,suspension culture,and hairy root culture. This study highlighted the influences of reactor type,culture system,precursor,elicitor type, and light wavelength on the suspension culture of S. involucrate cells. The chemical components of S. involucrata cells mainly include phenylpropanoids,flavonoids,lignans,and steroids,among which phenylpropanoids are the most abundant. S. involucrata cells have multiple pharmacological activities of anti-inflammation,analgesia,activating blood and resolving stasis,immunoregulation,increasing bone density,lowering blood lipids,anti-hypoxia,anti-exercise fatigue,anti-radiation,anti-obesity,and anti-oxidation. Moreover,it has the potential of treating aplastic anemia. This study reviews the cell culture technologies,chemical components,and pharmacological activities of S. involucrata cells,laying a basis for the further research,development,and utilization.

Systems Pharmacology-Based Dissection of Anti-Cancer Mechanism of Traditional Chinese Herb Saussurea involucrata.

Cancer has the highest mortality in humans worldwide, and the development of effective drugs remains a key issue. Traditional Chinese medicine Saussurea involucrata (SI) exhibits a series of effects, such as anti-cancer, but the action mechanisms are still unclear. Here, systems pharmacology was applied to reveal its anti-cancer mechanism. First, we screened the active compounds of SI. Then, the compound-target network, target-disease network, and target-pathway network were constructed. DAVID was applied for GOBP analysis and KEGG pathway enrichment analysis on cancer-related targets. Seven potential compounds and 187 targets were identified. The target-disease classification network showed that compounds mainly regulated proteins related to cancer, nervous system diseases, and cardiovascular system diseases. Also, SI anti-tumor effect mainly associated with the regulation of NO production, angiogenesis, MAPK, and PKB from GOBP enrichment. Additionally, KEGG pathway enrichment indicated that targets involved in anti-inflammatory action, inhibiting angiogenesis and anti-proliferation or inducing apoptosis. Experimental validation showed that four active compounds could inhibit cell proliferation and promote apoptosis in A549 (except for kaempferol), PC-3, and C6 cells. This study not only provides experimental evidence for further research on SI in cancer treatment but also promotes the development of potential drugs of SI in modern medicine.

Research progress on culture technologies,chemical components,and pharmacological activities of Saussurea involucrata cells / 中国中药杂志

Saussurea involucrata,a traditional Chinese medicinal material,is effective in the treatment of rheumatoid arthritis with cold-dampness blockage syndrome,cold pain in lower abdomen,and menstrual irregularities. However,due to the specific habitat,low natural reproduction rate,slow growth,and overexploitation,it is at the high risk of extinction. S. involucrata cells can be obtained through callus culture,suspension culture,and hairy root culture. This study highlighted the influences of reactor type,culture system,precursor,elicitor type, and light wavelength on the suspension culture of S. involucrate cells. The chemical components of S. involucrata cells mainly include phenylpropanoids,flavonoids,lignans,and steroids,among which phenylpropanoids are the most abundant. S. involucrata cells have multiple pharmacological activities of anti-inflammation,analgesia,activating blood and resolving stasis,immunoregulation,increasing bone density,lowering blood lipids,anti-hypoxia,anti-exercise fatigue,anti-radiation,anti-obesity,and anti-oxidation. Moreover,it has the potential of treating aplastic anemia. This study reviews the cell culture technologies,chemical components,and pharmacological activities of S. involucrata cells,laying a basis for the further research,development,and utilization.

A new sesquiterpenoid glycoside from Saussurea involucrata.

Saussurea involucrata, known for the abundant bioactive components, is a precious traditional Chinese medicine. In this study, a novel guaiane sesquiterpenoid glycoside named (1R, 5R, 6R, 7R, 8S, 11S)-11, 13-dihydrodehydrocostuslactone-8-O-6'-2''(E)-butenoyl-ß-D-glucopyranoside (1), together with seven known compounds (2-8) were isolated from the dried aerial part of S. involucrata. Their structures were elucidated by spectroscopic and physico-chemical analyses. The antioxidant and anti-inflammatory activities of compound 1 were investigated. And compound 1 showed weak radical scavenging activity and low inhibitory activity on nitric oxide (NO) production.

[Analysis of flavonoids and antitumor activity of transgenic Saussurea involucrate].

The aim of this paper was to investigate the flavonoids of callus of transgenic and non-transgenic Saussurea involucrate and its antitumor activity on the esophageal cancer CaEs-17 cells. The species and content of mono-phenols were detected by high performance liquid chromatography. The growth of human esophageal cancer CaEs-17 cells was detected using CCK-8 assay, apoptosis morphology observation and flow cytometry. Expression of related apoptotic genes Bax and Bcl-2 were determined by qPCR. The results showed that the content of total flavonoids in the transgenic callus was 2.72 times that of the non-transgenic callus. The cyanidin-galactoside was detected in the transgenic callus, but not in the non-transgenic callus. The inhibitory effect of the extracts from the transgenic callus on CaEs-17 cells was more significant than that of the non-transgenic callus, and the IC50 value had a decreased of 26.4%. Flow cytometry analysis results showed that the apoptosis induction effect of the extracts from the transgenic callus on CaEs-17 cells was significantly better than that of the non-transgenic callus. Fluorescence quantitative PCR analysis results showed that the extracts from the transgenic callus could up-regulate the expression of proapoptotic gene Bax and down-regulate the expression of apoptotic gene Bcl-2, and the regulation effect of the transgenic callus was more significant. Therefore, compared with the non-transgenic callus, the antitumor activity of the extracts from the callus of transgenic S. involucrate on the esophageal cancer CaEs-17 cells was significantly increased, which was closely related to the accumulation of cyanidin-galactoside and its metabolism-related flavonoid compounds in the transgenic callus.

Therapeutic effects of Saussurea involucrata injection against severe acute pancreatitis- induced brain injury in rats.

OBJECTIVES: To observe the therapeutic effects of Saussurea involucrata (Sau) injection against severe acute pancreatitis (SAP)-induced brain injury. METHODS: Sodium taurocholate-induced SAP-modeled rats were equally randomized into an SAP model group (SAP group) and a Sau treated group (Sau  +  S group). Healthy rats were equally randomized into a Sau treated group (Sau  +  H group) and a sham operation group (SO group). Serum amylase levels, endothelin-1 (ET-1) and nitric oxide (NO) contents were determined by optical turbidimetry, ELISA and nitrate reductase method respectively. Western blot was used to detect protein expression levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), ET-1, inducible nitric oxide synthase (iNOS) and endothelial NOS (eNOS) while mRNA levels of these biomarkers in brain tissue were measured by quantitative real-time PCR. Furthermore, pathological changes, as well as all above indexes of pancreas and brain, were observed at 6, 24 and 48 h after administration. RESULTS: There was a significant difference in mortality between SAP and Sau  +  S groups (P  <  0.05). Serum amylase levels, ET-1 and NO contents, ET-1/NO ratio, relative expression levels of ET-1 and iNOS protein/mRNA of brain tissue in Sau + S group were lower than those in SAP group at 24 and 48 h post-operation (P  <  0.05 or 0.01), meanwhile, pancreas and brain pathological scores showed similar tendency (P  <  0.01). However, both protein and mRNA levels of PI3K, Akt and eNOS of brain tissue in Sau + S group were higher than those in SAP group (P  <  0.05 or P  <  0.01). There were no significant differences in all indexes between Sau + H and SO groups at all designated time points (P  >  0.05). CONCLUSIONS: Sau injection has therapeutic effects on SAP-induced brain injury in rats.

Analysis of flavonoids and antitumor activity of transgenic Saussurea involucrate / 中国中药杂志

The aim of this paper was to investigate the flavonoids of callus of transgenic and non-transgenic Saussurea involucrate and its antitumor activity on the esophageal cancer CaEs-17 cells. The species and content of mono-phenols were detected by high performance liquid chromatography. The growth of human esophageal cancer CaEs-17 cells was detected using CCK-8 assay, apoptosis morphology observation and flow cytometry. Expression of related apoptotic genes Bax and Bcl-2 were determined by qPCR. The results showed that the content of total flavonoids in the transgenic callus was 2.72 times that of the non-transgenic callus. The cyanidin-galactoside was detected in the transgenic callus, but not in the non-transgenic callus. The inhibitory effect of the extracts from the transgenic callus on CaEs-17 cells was more significant than that of the non-transgenic callus, and the IC₅₀ value had a decreased of 26.4%. Flow cytometry analysis results showed that the apoptosis induction effect of the extracts from the transgenic callus on CaEs-17 cells was significantly better than that of the non-transgenic callus. Fluorescence quantitative PCR analysis results showed that the extracts from the transgenic callus could up-regulate the expression of proapoptotic gene Bax and down-regulate the expression of apoptotic gene Bcl-2, and the regulation effect of the transgenic callus was more significant. Therefore, compared with the non-transgenic callus, the antitumor activity of the extracts from the callus of transgenic S. involucrate on the esophageal cancer CaEs-17 cells was significantly increased, which was closely related to the accumulation of cyanidin-galactoside and its metabolism-related flavonoid compounds in the transgenic callus.

The complete chloroplast genome of Tianshan Snow Lotus (Saussurea involucrata), a famous traditional Chinese medicinal plant of the family Asteraceae.

abtract We decoded the complete chloroplast DNA (cpDNA) sequence of the Tianshan Snow Lotus (Saussurea involucrata), a famous traditional Chinese medicinal plant of the family Asteraceae, by using next-generation sequencing technology. The genome consists of 152 490 bp containing a pair of inverted repeats (IRs) of 25 202 bp, which was separated by a large single-copy region and a small single-copy region of 83 446 bp and 18 639 bp, respectively. The genic regions account for 57.7% of whole cpDNA, and the GC content of the cpDNA was 37.7%. The S. involucrata cpDNA encodes 114 unigenes (82 protein-coding genes, 4 rRNA genes, and 28 tRNA genes). There are eight protein-coding genes (atpF, ndhA, ndhB, rpl2, rpoC1, rps16, clpP, and ycf3) and five tRNA genes (trnA-UGC, trnI-GAU, trnK-UUU, trnL-UAA, and trnV-UAC) containing introns. A phylogenetic analysis of the 11 complete cpDNA from Asteracease showed that S. involucrata is closely related to Centaurea diffusa (Diffuse Knapweed). The complete cpDNA of S. involucrata provides essential and important DNA molecular data for further phylogenetic and evolutionary analysis for Asteraceae.

Inhibitory effects of Saussurea involucrata (Kar. et Kir.) Sch. -Bip. on adjuvant arthritis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Saussurea involucrate (Kar. et Kir.) Sch. -Bip is an endangered species of the Compositae family, and this species has long been used for the treatment of rheumatoid arthritis, dysmenorrhea, stomachache, and altitude sickness in Uighur folk and Chinese medicine. AIM OF THE STUDY: This study aimed to investigate the different therapeutic efficacy of alcohol infusion (SEI) and water decoction (SWD) of S. involucrata in treating rheumatoid arthritis using complete Freund's adjuvant (CFA)-induced arthritis (AA) in a rat model. MATERIALS AND METHODS: Male Wistar rats (160-180g) were immunized by intradermal injection of 0.1mL of CFA into the left hind metatarsal footpad. Aspirin was chosen as the positive drug. Alcohol infusion (SEI, 400 and 800mg/kg) and water decoction (SWD, 443 and 886mg/kg) of S. involucrata aerial parts were orally administered from day 1 and continued for 21 days. Arthritis severity was evaluated by arthritic score, body weight loss, and paw swelling. The levels of TNF-α, IL-ß, and IL-6 in the serum of AA rats were detected by enzyme linked immunosorbent assay (ELISA). Histological changes in the ankle joint were also analyzed in the AA rats. RESULTS: Both SEI and SWD significantly ameliorated AA severity, as suggested by the modulatory effects on body weight loss, paw swelling, and arthritic score. Histopathological improvement in the joint architecture was also observed in the SEI- and SWD-treated AA rats. The overproduction of TNF-α, IL-1ß, and IL-6 was remarkably attenuated in the serum of all treated rats. Furthermore, the therapeutic effect of SWD was more potent than that of SEI in treating rheumatoid arthritis using AA in a rat model, which was reported for the first time. CONCLUSIONS: These results suggested that the extract of S. involucrata significantly attenuated adjuvant arthritis in rats by decreasing the levels of TNF-α, IL-1ß, and IL-6 in the serum. S. involucrata has the potential to be regarded as a candidate for the treatment of human arthritis. Moreover, the therapeutic effect of SWD was much better than alcohol infusion, indicting that active constituents are mainly in the water extract, which is helpful for the clinical treatments to choose the appropriate process.

Saussurea involucrata: A review of the botany, phytochemistry and ethnopharmacology of a rare traditional herbal medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Saussurea involucrata Matsum. & Koidz. is an endangered species of the Asteraceae family, growing in the high mountains of central Asia. It has been, and is, widely used in traditional Uyghur, Mongolian and Kazakhstan medicine as well as in Traditional Chinese Medicine as Tianshan Snow Lotus (Chinese: ). In traditional medical theory, S. involucrata can promote blood circulation, thereby alleviating all symptoms associated with poor circulation. It also reputedly eliminates cold and dampness from the body, diminishes inflammation, invigorates, and strengthens Yin and Yang. It has long been used to treat rheumatoid arthritis, cough with cold, stomach ache, dysmenorrhea, and altitude sickness in Uyghur and Chinese medicine. AIM OF THE REVIEW: To comprehensively summarize the miscellaneous research that has been done regarding the botany, ethnopharmacology, phytochemistry, biological activity, and toxicology of S. involucrata. METHOD: An extensive review of the literature was carried out. Apart from different electronic databases including SciFinder, Chinese National Knowledge Infrastructure (CNKI), ScienceDirect that were sourced for information, abstracts, full-text articles and books written in English and Chinese, including those traditional records tracing back to the Qing Dynasty. Pharmacopoeia of China and other local herbal records in Uighur, Mongolian and Kazakhstan ethnomedicines were investigated and compared for pertinent information. RESULTS: The phytochemistry of S. involucrata has been comprehensively investigated. More than 70 compounds have been isolated and identified; they include phenylpropanoids, flavonoids, coumarins, lignans, sesquiterpenes, steroids, ceramides, polysaccharides. Scientific studies on the biological activity of S. involucrata are equally numerous. The herb has been shown to have anti-neoplastic, anti-inflammatory, analgesic, anti-oxidative, anti-fatigue, anti-aging, anti-hypoxic, neuroprotective and immunomodulating effects. Many have shown correlations to the traditional clinical applications in Traditional Chinese Medicine and medicines. The possible mechanisms of S. involucrata in treating various cancers are revealed in the article, these include inhibition of cancer cells by affecting their growth, adhesion, migration, aggregation and invasion, inhibition of epidermal growth factor receptor signaling in cancer cells, hindrance of cancer cell proliferation, causing cytotoxicity to cancer cells and promoting expression of tumor suppressor genes. Dosage efficacy is found to be generally concentration- and time-dependent. However, studies on the correlation between particular chemical constituents and specific bioactivities are limited. CONCLUSION: In this review, we have documented the existing traditional uses of S. involucrata and summarized recent research into the phytochemistry and pharmacology of S. involucrata. Many of the traditional uses have been validated by phytochemical and modern pharmacological studies but there are still some areas where the current knowledge could be improved. Although studies have confirmed that S. involucrata has a broad range of bioactivities, further in-depth studies on the exact bioactive molecules and the mechanism of action are expected. Whether we should use this herb independently or in combination deserves to be clarified. The exact quality control as well as the toxicology studies is necessary to guarantee the stability and safety of the clinic use. The sustainable use of this endangered resource was also addressed. In conclusion, this review was anticipated to highlight the importance of S. involucrata and provides some directions for the future development of this plant.

A new polyphenol, 1, 3-di-O-caffeoyl-5-O-(1-methoxyl-2-O-caffeoyl-4-maloyl)-quinic acid, isolated from cultured cells of Saussurea involucrata.

The present study was designed to isolate the polyphenol constituents of cultured cells of Saussurea involucrata. The polyphenol type constituents were isolated using chromatography methods, and then characterized by spectral analysis. 1,1-Diphenyl-2-picrylhydrazyl radical 2,2-Diphenyl-1-(2,4,6-trinitrophenyl)-hydrazyl (DPPH) and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) free radical scavenging were assayed using Vitamin C as the positive control. One new polyphenol 18, 1, 3-di-O-caffeoyl-5-O-(1-methoxyl-2-O-caffeoyl-4-maloyl)-quinic acid, together with 17 known compounds, was isolated and characterized. In conclusion, Compound 18 was a new caffeoyl maloyl quinic acid type polyphenol and showed desired vitro anti-oxidant activity. Compounds 1-5, 9, 10, 14, 15, and 17 were isolated from cultured cells of Saussurea involucrata for the first time.

In vitro culture and production of syringin and rutin in Saussurea involucrata (Kar. et Kir.) - an endangered medicinal plant.

BACKGROUND: Saussurea involucrata (Kar. et Kir.) commonly known as 'snow lotus' or 'Xue Lian' is an important plant in the traditional Chinese system of medicine. The plant contains flavonoids such as syringin and rutin. These compounds have been reported to be anti-rheumatic, anti-inflammatory and dilate blood vessels, lower blood pressure, prevent cardiovascular diseases, enhance immunity, and act as anti-aging, anti-cancer, and anti-fatigue agents. The species has become endangered due to the excessive collection of S. involucrata plants in the wild, slower plant growth and ecological destruction of natural habitats. There is a severe shortage of plant material, while the market demand is ever increasing. Hence, it is very important to apply tissue culture technique for plant propagation and production of the bioactive compounds of this species. RESULTS: Multiple shoot induction and proliferation in shoot base explants derived from in vitro raised seedlings of S. involucrata was achieved on 3/4 strength of Murashige and Skoog's (MS) basal medium (MSBM) supplemented with 1.0 mg/L-1 BA and 1.5 mg/L-1 NAA. Rooting was induced in 100 % shoots cultured on 1/2X MSBM supplemented with 1.0 mg/L-1 IBA for one week and then transfer to auxin free medium. The plantlets could be acclimatized successfully by sachet technique and established in the greenhouse. Maximum callus induction and proliferation in leaf segments was achieved on 1/2X MSBM supplemented with 0.5 mg/L-1 BA, 0.5 mg/L-1 NAA, 0.4 % gelrite and on incubation at 20 °C. Container closures had an influence on the quality and quantity of callus and production of the active compounds. The HPLC analysis showed much higher syringin content in in vitro shoots and callus as compared to commercially available market crude drug. CONCLUSION: The present study describes an in vitro culture protocol of Saussurea involucrata. The bioactive compounds, syringin and rutin could be produced through tissue culture technique without sacrificing the endangered Saussurea involucrata plants in the wild.