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Liquid chromatography coupled with diode array detector and electrospray ionization mass spectrometry was developed for the qualitative and quantitative comparison of the main constituents in Saussurea laniceps (SL) and S. medusa (SM), two species of plants used under the name "Xuelianhua" in traditional Tibetan medicine. A method validation including linearity, limit of detection, precision and recovery was performed. The results showed that a good linearity with R<sup>2</sup> &gt; 0.99 was achieved, and the limit of detection of the quantified constituents was reported to be between 0.8 and 3.3 ng. The relative standard deviation value was below 3.82% for repeatability, and recovery studies for the quantified compounds were found to be within the range 90.92-103.12%. The unique properties of the present method were evaluated by analyzing twelve related herbal samples including five S. laniceps samples and seven S. medusa samples. Twenty-two compounds including phenolic acids, cumarins, lignanoids and flavonoids were identified by online ESI-MS and by comparison with literature data and standard compounds, and seven of them were quantified by LC-DAD simultaneously. The results demonstrated that the common constituents in the two herbs were protocatechuic acid, syringoside, chlorogenic acid, isoquercitroside, 1,5-dicaffeoylquinic acid, apigenin 7-O-Îø-d-glucoside, chrysoeriol 7-O-Îø-d-glucoside, acacetin 7-O-Îø-d-glucoside, apigenin and chrysoeriol. In the present study, it was found that the characteristic constituents were umbelliferone, scopoletin and their glucosides in S. laniceps, as well as arctiin and arctigenin in S. medusa. It was feasible to choose these characteristic compounds for the quality evaluation as well as chemical authentication of the two related herbs. The results also support discrimination between the two species when using them in folk medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Saussurea involucrata (Kar. et Kir.) Sch.-Bip. (Compositae) has long been used under the herbal name "Snow Lotus" for the treatment of rheumatoid arthritis, stomachache and dysmenorrhea in Uighur folk medicine. In traditional Tibetan medicine, Saussurea laniceps Hand.-Mazz. and Saussurea medusa Maxim. have also been used under the name "Snow Lotus" and prescribed for the treatment of pain and inflammatory conditions.AIM OF THE STUDY: The present study evaluated the pharmacological effects of three species of "Snow Lotus" in experimental inflammation and pain models, and determined the chemical compounds that may correlate with their pharmacological activities. MATERIALS AND METHODS: The anti-inflammatory activities of the three herbs were observed by using carrageenan-induced paw edema in rats and xylene-induced ear edema in mice. Investigations on the analgesic effects were conducted, including acetic acid-induced writhing and hot-plate test. An UPLC-MS method was developed to analyze the chemical composition of the three herbs and of plasma samples after herb administration. RESULTS: In rat paw edema model, the peak inhibitory effects of Saussurea laniceps and Saussurea involucrata (55.1% and 42.2%, respectively) were recorded with the dose of 400mg/kg at 3h post-carrageenan injection. In mouse ear edema model, oral administration of Saussurea laniceps, Saussurea involucrata and Saussurea medusa extract (400mg/kg) resulted in a significant inhibition of ear edema by 40.9%, 33.3%, and 9.1%, respectively. In the writhing test, oral administration of Saussurea laniceps extract (100, 200 and 400mg/kg) resulted in a significant inhibition of writhings by 13.5%, 22.3%, and 43.5%, respectively. In the hot-plate test, Saussurea laniceps extract significantly increased the latency of jumping response by 38.2% and 52.7% when treated orally at 200 and 400mg/kg in mice, respectively. Flavonoids, coumarins and lignins were found to be present in plasma after administration of the extracts and may be the basis of the observed pharmacological effects. CONCLUSION: The results clearly demonstrated that Saussurea laniceps was most effective; Saussurea involucrata exhibited a moderate potency, whereas Saussurea medusa possessed little effect against the experimental edema and pains. This study also supported discrimination among the three herbs when using them in folk medicine.

The present study evaluated the pharmacological effects of three species <b>Saussurea</b> commonly used as the traditional herbal drug “Snow Lotus” in experimental inflammation and pain models, and determined the chemical compounds that may correlate with their pharmacological activities. The results clearly demonstrated that <b>Saussurea laniceps</b> was most effective; <b>Saussurea involucrata</b> exhibited a moderate potency, whereas <b>Saussurea medusa</b> possessed little effect against the experimental edema and pains. Flavonoids, coumarins and lignins were found to be present in plasma after administration of the extracts and may be the basis of the observed pharmacological effects.<br>Ethnopharmacological relevance: <b>Saussurea involucrata</b> (Kar. et Kir.) Sch.-Bip. (Compositae) has long been used under the herbal name “Snow Lotus” for the treatment of rheumatoid arthritis, stomachache and dysmenorrhea in Uighur folk medicine. In traditional Tibetan medicine, <b>Saussurea laniceps</b> Hand.-Mazz. and <b>Saussurea medusa</b> Maxim. have also been used under the name “Snow Lotus” and prescribed for the treatment of pain and inflammatory conditions.<br>Aim of the study: The present study evaluated the pharmacological effects of three species of “Snow Lotus” in experimental inflammation and pain models, and determined the chemical compounds that may correlate with their pharmacological activities.<br>Materials and methods: The anti-inflammatory activities of the three herbs were observed by using carrageenan-induced paw edema in rats and xylene-induced ear edema in mice. Investigations on the analgesic effects were conducted, including acetic acid-induced writhing and hot-plate test. An UPLC-MS method was developed to analyze the chemical composition of the three herbs and of plasma samples after herb administration.<br>Results: In rat paw edema model, the peak inhibitory effects of <b>Saussurea laniceps</b> and <b>Saussurea involucrata</b> (55.1% and 42.2%, respectively) were recorded with the dose of 400 mg/kg at 3 h post-carrageenan injection. In mouse ear edema model, oral administration of <b>Saussurea laniceps</b>, <b>Saussurea involucrata</b> and <b>Saussurea medusa</b> extract (400 mg/kg) resulted in a significant inhibition of ear edema by 40.9%, 33.3%, and 9.1%, respectively. In the writhing test, oral administration of <b>Saussurea laniceps</b> extract (100, 200 and 400 mg/kg) resulted in a significant inhibition of writhings by 13.5%, 22.3%, and 43.5%, respectively. In the hot-plate test, <b>Saussurea laniceps</b> extract significantly increased the latency of jumping response by 38.2% and 52.7% when treated orally at 200 and 400 mg/kg in mice, respectively. Flavonoids, coumarins and lignins were found to be present in plasma after administration of the extracts and may be the basis of the observed pharmacological effects.<br>Conclusion: The results clearly demonstrated that <b>Saussurea laniceps</b> was most effective; <b>Saussurea involucrata</b> exhibited a moderate potency, whereas <b>Saussurea medusa</b> possessed little effect against the experimental edema and pains. This study also supported discrimination among the three herbs when using them in folk medicine.

Ethnopharmacological relevance: Saussurea laniceps Hand.-Mazz. (SL) has long been used under the herbal name Tibetan 'Snow Lotus' for the treatment of rheumatoid arthritis, stomachache and dysmenorrhea in Tibetan folk medicine. Since herbal medicine (HM) is a synergistical system with multiple components, both of the metabolism and pharmacokinetic studies of HM are interdependent. This study aimed to develop an integrated strategy based on the UPLC-DAD-QTOF-MS technique for metabolism and pharmacokinetic studies of HM.Material and methods: SL was used here as a test herb to verify the feasibility of the proposed strategy. SL was administered to rats, then, the blood plasma, urine and feces were analyzed to determine the metabolic profiles. Using our strategy, umbelliferone and scopoletin were evaluated to be the key bioactive components. Their pharmacokinetic parameters were measured and biotransformation pathways were elucidated.Results: After oral administration of SL to rats, 17 components in blood, 10 components in urine and 2 components in feces were identified and characterized using our UPLC-DAD-QTOF-MS method. Umbelliferone, scopoletin and their metabolites were found to be the major components involved in the metabolism process. Literature reports also suggest that umbelliferone and scopoletin are responsible for the therapeutic effects of SL, thus these two components were selected as the active markers for pharmacokinetic study. In the test of validity, the established method presented good linearity with R-2> 0.99. The relative standard deviation value was below 13.9% for precision, and recovery studies for accuracy were found to be within the range 91.8-112.5%.Conclusion: The present strategy offers, simultaneously, precision in quantitative analysis (metabolism study) and accuracy in quantitative analysis (pharmacokinetic study) with greater efficiency and less costs, which is therefore reliably used for integrated metabolism and pharmacokinetic studies of HM. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

<i>Saussurea laniceps</i> (Compositae), commonly known as “cotton-headed snow lotus”, is the most effective “snow lotus” used in both Tibetan and Chinese folk medicine. It performs outstandingly in treating rheumatoid arthritis, which mainly is credited for its anti-inflammatory and anti-nociceptive efficacy, as explained by modern pharmacological studies. Extracts of the herb, including umbelliferone and scopoletin, exert such effects in various in vivo and in vitro studies. Besides the two chemicals above, more than 100 organic compounds have been found in <i>S. laniceps</i>, and 58 of them are presented here in molecular structure, including cynaropicrin, mokko lactone, apigenin, acacetin, and luteolin, all contributing to different bioactivities, such as analgesic, antioxidant, immunomodulatory, anti-microbial and anticancer effects. We provide a natural product library of <i>S. laniceps</i>, giving inspirations for structure modification and bioactivity-oriented screening, enabling sustainable use of this valuable plant. The ethnomedical applications and pharmacological discoveries are compared and crosslinked, revealing modern evidence for traditional usages. Despite that <i>S. laniceps</i> is a representative “snow lotus” herb, its material medica records and clinical applications are complicated; there is considerable confusion with the different snow lotuses in the academic community and on the market. This review also aims at clearing such confusion, and improving quality assessment and control of the herb. To better utilize the valuable plant, further comparison among the chemical constitutions, pharmacological activities and therapeutic mechanisms of different snow lotuses are needed.