[Optimization of processing technology of bark of Ilicis Rotundae Cortex based on quality by design concept].

Based on the concept of quality by design(QbD), this study optimized the processing technology of Ilicis Rotundae Cortex. According to the processing method and ingredient requirements of Ilicis Rotundae Cortex in the Chinese Pharmacopoeia, the content of syringin and pedunculoside, alcohol extract, fragmentation rate, and moisture content were taken as the critical quality attributes(CQAs). The soaking time, moistening time, and drying time were taken as critical process parameters(CPPs) by single factor tests. The weight coefficients of CQAs were determined by the analytic hierarchy process(AHP)-entropy weighting method, and the comprehensive score was calculated. With the comprehensive score as the response value, Box-Behnken design was employed to establish a mathematical model between CPPs and CQAs, and the design space for the processing of Ilicis Rotundae Cortex was built and verified. The results of ANOVA showed that the mathematical model had the P value below 0.05, the lack of fit greater than 0.05, adjusted R~2=0.910 5, and predicted R~2=0.831 0, which indicated that the proposed model had statistical significance and good prediction performance. Considering the factors in production, the best processing conditions of Ilicis Rotundae Cortex were decoction pieces of about 1 cm soaking for 1 h, moistening for 4 h, and drying at 60-70 ℃ in a blast drier for 2 h. The optimized processing technology of Ilicis Rotundae Cortex was stable and feasible, which can provide a reference for the standardized preparation and stable quality of Ilicis Rotundae Cortex.

A systematic review: Botany, phytochemistry, traditional uses, pharmacology, toxicology, quality control and pharmacokinetics of Ilex rotunda Thunb.

ETHNOPHARMACOLOGICAL RELEVANCE: Ilex rotunda Thunb. (I. rotunda) is an Ilex species of Aquifoliaceae, widely distributed in East Asia. Its dried bark is commonly used as a medicinal part in the field of traditional Chinese medicine (TCM), named Ilicis Rotundae Cortex. This medicinal plant is commonly used for clearing heat and removing toxin, draining dampness and relieving pain in TCM to treat tonsillitis, acute gastroenteritis, gastric and duodenal ulcer, rheumatism, traumatic injury, and so on. It also has significant development value on lipid-lowering, hepatoprotection and anti-inflammation, but the potential mechanism needs to be further explored. AIM OF THE REVIEW: More and more medicinal substances are being discovered in I. rotunda with multiple biological activities, which help to advance the ethno-pharmacological research in I. rotunda. However, to date there is a lack of a systematic summary of research progress on I. rotunda. This review aims to provide a critical summary of the current studies on I. rotunda. The progress in research on botany, phytochemistry, traditional uses, pharmacology, toxicology, quality control and pharmacokinetics of the plant is discussed. It hopes to provide useful references and guidance for the future directions of research on I. rotunda. MATERIALS AND METHODS: Studies of I. rotunda were collected via Google Scholar and Baidu Scholar, PubMed, ScienceDirect, SciFinder, Web of Science, China National Knowledge Infrastructure (CNKI), WANFANG DATA and libraries. Some local books, official websites, PhD or MS's dissertations were also included. The literature cited in this review covered the period from 1956 to January 2022. RESULTS: Analysis of the literature indicates that I. rotunda is a potentially valuable herbal medicine for the therapeutic of various diseases. To date, 120 compounds were found and identified in I. rotunda, mainly including triterpenoids, phenylpropanoids, etc. Modern pharmacological studies also found that the plant has the activities of protecting the cardiovascular system, lowering lipids and protecting the liver, as well as being an anti-inflammatory, anti-tumor and antibacterial. CONCLUSIONS: This review summarizes the results from current studies of I. rotunda. However, the current explanation seems insufficient and unsatisfactory, in terms of the relationships between the traditional uses and the modern pharmacological activities, the mechanisms and the material basis. Thus, a critical and comprehensive evaluation is necessary to explore its future research prospects and development direction.

UPLC/Q-TOF-MS/MS-based metabolomics revealed the lipid-lowering effect of Ilicis Rotundae Cortex on high-fat diet induced hyperlipidemia rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Ilicis Rotundae Cortex (IRC), a Chinese crude drug, has been widely utilized in Guangdong and Guangxi provinces of China to treat or prevent cardiovascular diseases. AIM OF STUDY: This investigation aims to study the lipid-lowering effect of IRC, as well as the regulating effect on the endogenous metabolites in hyperlipidemia rats. MATERIALS AND METHODS: High-fat diet induced hyperlipidemia rats were administrated with different doses of IRC extract (0.5, 1.0 and 2.0 g/kg/day) for 5 weeks. Simvastatin was used as the positive control. Body weight, serum lipid levels and histopathology of liver were evaluated. The metabolic profiles of plasma, urine and cecum content were analyzed using UPLC/Q-TOF-MS/MS-based metabolomics approach coupled with multivariate data analysis. RESULTS: The levels of serum TC, TG, LDL-C, AST and ALT were significantly decreased and HDL-C level was increased in IRC treatment groups. The hepatic histomorphology was partially restored. 23, 26 and 15 metabolites in plasma, urine and cecum content were determined as the biological biomarkers, respectively. IRC extract could partially recover the disturbed metabolic pathways of bile acid metabolism, linoleic acid metabolism, arachidonic acid metabolism, taurine and hypotaurine metabolism, glyoxylate and dicarboxylate metabolism, glycerophospholipid metabolism, synthesis and degradation of ketone bodies, sphingolipid metabolism and riboflavin metabolism. CONCLUSION: This study demonstrated that IRC could effectively improve the serum lipids and partially restore the hepatic histomorphology. The underlying metabolic mechanism mainly included improving the metabolism of bile acids, glycerophospholipid, sphingolipid, fatty acid and amino acid. This is the first study on the lipid-lowering effect of IRC from the perspective of metabolomics.

Rapid profiling and pharmacokinetic studies of multiple potential bioactive triterpenoids in rat plasma using UPLC/Q-TOF-MS/MS after oral administration of Ilicis Rotundae Cortex extract.

Triterpenoids, the major bioactive ingredients of Ilicis Rotundae Cortex, contributes a significant cardiovascular protection activity. Although many studies about the total saponins have been reported, the absorption triterpenoids and pharmacokinetic behaviors were unclear. Thus, the present study aims to comprehensive elucidate the absorption triterpenoids and their pharmacokinetics in rats after oral administration the crude extract using UPLC/Q-TOF-MS/MS. A total of forty-two triterpenoids were successfully characterized from the rat plasma, and thirty-two of them were validated by the reference substances, while the others were tentatively identified based on the mass spectral fragmental patterns. Furthermore, the plasma concentrations of six absorption bioactive triterpenoids (rotundinoside C, ilexoside O, pedunculoside, rotundic acid, rotundanonic acid and ilexgenin A) were simultaneously quantified by selected reaction monitoring in negative ionization mode. All analytes exhibited good linearity with correlation coefficients values greater than 0.99 and the LLOQ ranged from 1.2 to 3.2 ng/mL, and method validation for selectivity, precision, accuracy, recovery, matrix effect and stability were reckoned acceptable. The results were successfully applied for the multiple-component pharmacokinetic study of the six bioactive triterpenoids.

Preparation of Rotundic Acid Monomer and Content Determination of 3 Components in Ilicis rotundae and Its Refined Products by RP-HPLC / 中国药房

OBJECTIVE: To prepare high-purity rotundic acid, and to determine the contents of syringoside, peduncloside and rotundic acid in Ilicis rotundae and its refined products. METHODS: I. rotundae saponins was prepared by ethanol extraction method and hydrolyzed with methanol and sodium hydroxide; rotundic acid monomer was obtained after recrystallization. The contents of syringoside, peduncloside and rotundic acid in I. rotundae, its refined product 1 and its refined product 2 were determined by RP-HPLC. The determination was performed on an Agilent XDB C18 column with mobile phase consisted of water-acetonitrile (gradient elution) at the flow rate of 1. 2 mL/min. The column temperature was 30 ℃, and the detection wavelength was set at 210 nm. The sample size was 10 μL. RESULTS: The purity of rotundic acid exceeded 99％. The linear ranges of syringing, peduncloside and rotundic acid were 0. 18-3. 22, 0. 59-10. 36 and 0. 20-3. 53 μg, respectively (r=0. 999 9). RSDs of precision, stability (24 h) and reproducibility tests were all lower than 2. 0％ (n=6-7). The average recoveries were 96. 08％-100. 81 ％ (RSD≤1. 98％, n=6). The contents of syringoside,peduncloside and rotundic acid in I. rotundae were 1. 61％,7. 26％, 1. 29％ (RSD≤1. 08％,n=3); those of refined product 1 were 0,82. 59％,4. 18％ (RSD≤1. 67％,n=3); those of refined product 2 were 0, 73. 29％, 7. 41％ (RSD≤1. 15％,n=3),respectively. CONCLUSIONS: Prepared rotundic acid has high purity and is simple in preparation, safe and environmentally-friendly. RP-HPLC method that established is simple and reliable, and can meet the requirements for rapid analysis of I. rotundae and its refined products.

Identification of Ilicis Rotundae Cortex and Its Adulterant Based on HPLC Fingerprint / 中国中医药信息杂志

Objective To establish HPLC fingerprints for the identification of Ilicis Rotundae Cortex (Jiubiying), dried bark of Ilex rotunda Thunb., and its adulterant, dried bark of Ilex godajam (Colebr.) Wall.. Methods Some samples named Jiubiying were collected from some medicine markets and drugstores. The HPLC fingerprints were obtained to detect Jiubiying and Ilex godajam. The software Similarity Evaluation System of Chromatographic Fingerprints of Traditional Chinese Medicine (2004A edition) was used to evaluate fingerprints. Results The fingerprints of Jiubiying and Ilex godajam were established. Methodological study met the technical requirements of fingerprints. There were 31 and 28 common peaks in Jiubiying and Ilex godajam, respectively. Jiubiying and Ilex godajam could be classified into two clusters by principal component analysis and hierarchical clustering analysis. Conclusion Jiubiying and Ilex godajam can be identified by HPLC fingerprints. This method can provide an effective method for quality evaluation of Jiubiying.

Quality Evaluation of Cortex Ilicis Rotundae Medicinal Materials / 广州中医药大学学报

Objective To investigate and evaluate the quality of Cortex Ilicis Rotundae medicinal materials in Chinese herbal medicine market. Methods Twenty-two batches of Cortex Ilicis Rotundae commercial medicinal materials were identified and analyzed by characteristic identification, microscopic identification, thin layer chromatography ( TLC) and extractives determination, and the contents of syringin and pedunculoside were detected by high performance liquid chromatography (HPLC) according to the Chinese Pharmacopoeia published in 2010. And then the quality of the medicinal material of Cortex Ilicis Rotundae was evaluated comprehensively. Results Of the 22 batches of Cortex Ilicis Rotundae medicinal materials, 2 batches were adulterated with fake Cortex Ilicis Rotundae, one batch was inferior and was mixed with counterfeits, and the quality of 12 batches was also poor. Conclusion At present, the quality of Cortex Ilicis Rotundae medicinal materials in Chinese herbal medicine market varies greatly, and adulterants and the inferior are common.