Selection and evaluation of quality markers (Q-markers) of vladimiriae radix extract for cholestatic liver injury based on spectrum-effect relationship, pharmacokinetics, and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: As a representative local medicinal herb produced in China, Vladimiriae Radix (VR) has been proven to exert hepatoprotective and choleretic effects, with particular therapeutic efficacy in cholestatic liver injury (CLI), as demonstrated by the VR extract (VRE). However, the quality markers (Q-markers) of VRE for the treatment of CLI remain unclear. AIM OF THE STUDY: A new strategy based on the core element of "efficacy" was proposed, using a combination of spectrum-effect relationship, pharmacokinetics, and molecular docking methods to select and confirm Q-markers of VRE. MATERIAL AND METHODS: First, the HPLC fingerprinting of 10 batches of VRE was studied, and the in vivo pharmacological index of anti-CLI in rats was determined. The spectrum-effect relationship was utilized as a screening method to identify the Q-markers of VRE. Secondly, Q-markers were used as VRE pharmacokinetic markers to measure their concentrations in normal and CLI rat plasma, and to analyze their disposition. Finally, molecular docking was utilized to predict the potential interaction between the identified Q-markers and crucial targets of CLI. RESULTS: The fingerprints of 10 batches of VRE was established. The in vivo pharmacological evaluation of rats showed that VRE had a significant therapeutic effect on CLI. The spectrum-effect correlation analysis showed that costunolide (COS) and dehydrocostus lactone (DEH) were the Q-markers of VRE anti-CLI. The pharmacokinetic results showed that AUC(0-t), Cmax, CLZ/F, and VZ/F of COS and DEH in CLI rats had significant differences (P < 0.01). They were effectively absorbed into the blood plasma of CLI rats, ensuring ideal bioavailability, and confirming their role as Q-markers. Molecular docking results showed that COS, DEH had good affinity with key targets (FXR, CAR, PXR, MAPK, TGR5, NRF2) for CLI treatment (Binding energy < -4.52 kcal mol-1), further verifying the correctness of Q-marker selection. CONCLUSIONS: In this study, through the combination of experimental and theoretical approaches from the aspects of pharmacodynamic expression, in vivo process rules, and interaction force prediction, the therapeutic effect of VRE and Q-markers (COS、DEH) were elucidated. Furthermore, a new idea based on the principle of "efficacy" was successfully proposed for screening and evaluating Q-markers.

Synergistic effect of berberine hydrochloride and dehydrocostus lactone in the treatment of ulcerative colitis: Take gut microbiota as the target.

Ulcerative colitis (UC) is a difficult-to-cure and recurrent inflammatory bowel disease, and it is difficult to maintain long-term results with a single drug. Inspired by clinical medication in traditional Chinese medicine, we used berberine hydrochloride (BBH) and dehydrocostus lactone (DEH) in combination for the first time and focused on studying their mechanism of treating UC based on gut microbiota. Therefore, we evaluated the therapeutic effects of BBH and DEH on DSS-induced UC mice using ELISA, HE and AB-PAS staining, 16s rDNA amplicon sequencing technology, and fecal transplantation experiments (FMT). In this study, the combination of BBH and DEH significantly relieved symptoms, colonic inflammation, and intestinal barrier damage of DSS-induced UC mice, and they did not show antagonism. In addition, the co-administration of BBH and DEH altered the composition and function of gut microbiota, with BBH increasing the abundance of key beneficial bacterial genus Akkermansia and DEH aiming to enhance species diversity and supplying intestinal proteins to prevent overconsumption. Furthermore, our data showed that BBH and DEH improve the levels of short-chain fatty acids, which also proved the positive regulation of gut microbiota by BBH and DEH. Finally, the FMT confirmed the strong correlation between BBH, DEH, and the gut microbiota. In conclusion, the co-administration of BBH and DEH protected the intestinal barrier and reduced inflammatory damage by regulating gut microbiota, targeting the key beneficial bacterial genus Akkermansia, and maintaining a normal supply of intestinal proteins.

Comprehensive quality evaluation of two different geography originated Angelica sinensis Radix based on potential production area development and resource protection.

Angelica sinensis Radix (ASR) is mainly produced in the southern region of Gansu, China, and is a famous edible and medicinal herb. Noticeably, Aba region in Sichuan, China has similar geographical and climatic conditions to the southern region of Gansu, China, and has the potential to further develop the ASR planting industry chain. This study was the first to use an innovative method that combines GC-MS, HPLC-DAD fingerprints, and stoichiometric analysis to compare and explore the feasibility of using the Aba region as a source of high-quality ASR supplements. GC-MS analysis showed that the composition of ASR essential oil(AEO) in these two regions was highly similar (>99%). The HPLC data showed that the main sources of differences in ASR components between the two regions were coniferyl ferulate, E-ligustilide, Z-ligustilide, and Butylidenephthalide, which have great potential in anti-depression, regulating gut microbiota, and other aspects. The ASR in Aba region was rich in these components, and its biological activity might be higher to some extent than that in southern Gansu. This study confirmed the potential of the Aba region in Sichuan to become a high-quality production area for ASR, which was conducive to the expansion of ASR resources and the development of related industrial chains.

Polygonati Rhizoma with the homology of medicine and food: A review of ethnopharmacology, botany, phytochemistry, pharmacology and applications.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonati Rhizoma (PR), which contains rich national cultural connotations, is a traditional Chinese medicine with homology of medicine and food. It has been used for a long time as a tonic in China's multi-ethnic medical system, and is also used to treat diseases such as premature graying hair, deficiency of blood and essence, diabetes, hypertension, etc. Meanwhile, PR is often used as food in China, India, South Korea and other Asian countries, which can satisfy hunger and provide many health benefits. AIM OF THE REVIEW: This paper systematically reviewed the ethnopharmacology, botany, phytochemistry, pharmacology and related applications research of PR, and provided a reference for the comprehensive applications of PR, including basic research, product development and clinical applications. This paper also refined the national application characteristics of PR, such as rich plant resources, special chemical components and anti-hidden hungry, which laid a foundation for its high value and high connotation development in the future. MATERIALS AND METHODS: The literature information was collected systematically from the electronic scientific databases, including PubMed, Science Direct, Google Scholar, Web of Science, Geen Medical, China National Knowledge Infrastructure, as well as other literature sources, such as classic books of herbal medicine. RESULTS: A comprehensive analysis of the above literature confirmed that PR has been used in the ethnic medicine system of Asian countries such as China for thousands of years. In this paper, 12 species including official species that can be used as PR are summarized, which provide rich plant resources for PR. The chemical components in PR are divided into nutritional components and active components. The former not only contains non-starch polysaccharides and fructo-oligosaccharides, which account for about 50% in PR and are recognized as high-quality diet in the world, but also contains inorganic elements and mineral elements. And a total of 199 kinds active ingredients, including saponins, flavonoids, alkaloids, etc., were sorted out by us. The above ingredients make PR have a special property of anti-hidden hunger. Studies have shown that PR has a wide range of pharmacological activities, such as immune regulation, blood glucose regulation, lipid-lowering, antioxidant, anti-tumor, antibacterial, etc. It has been widely used in medicine, food, cosmetics, gardens and other fields. CONCLUSIONS: PR, as a classic medicinal material of the same origin, is widely used in the traditional ethnic medicine system. It contains abundant potential plant resources, chemical components and pharmacological activities. This paper also suggests that PR with high application value in food industry, has the potential to become a high-quality coarse grain. Exploring the way of grain and industrialization of PR is beneficial to fully develop the economic value of PR.

Mushroom-brush transitional conformation of mucus-inert PEG coating improves co-delivery of oral liposome for intestinal metaplasia therapy.

The blocking of gastric mucosal intestinal metaplasia (IM) has been considered to be the pivotal method to control the occurrence of gastric cancer. However, there is still a lack of effective therapeutic agent. Here, we developed mucus-penetrating liposome system by covering surface with polyethylene glycol (PEG) chains (hydrophilic and electroneutral mucus-inert material) to co-delivery candidate drugs combination. Then studied the impact on the transmucus performance of different conformations, which were constructed by controlling the density of PEG chains on the surface. The results showed that the particle size of 5%PEG-Lip was less than 120 nm, the polydispersity index was less than 0.3, and the surface potential tended to be neutral. The D value (long chain spacing) of 5% PEG-Lip was 3.25 nm, which was close to the RF value (diameter of spherical PEG long chain group without external force interference) of 3.44 nm, and the L value (extended length) was slightly larger than 3.44 nm. In this case, PEG showed mushroom-brush transitional conformation on the surface of liposomes. This conformation was not only promoted stable delivery, but also shielded the capture of mucus more favorably, leading to a more unrestricted transportation in mucus. The further in vivo experimental results demonstrated the rapid distribution of liposomes, which gradually appeared both in the superficial and deep glandular of mucosa and gland cells at 1 h and absorbed into the cell cytoplasm at 6 h. The 5% PEG-Lip with the mushroom-brush transitional configuration recalled abnormal organ index and improved inflammation and intestinal metaplasia. The modified PEG conformation assay presented here was more suitable for liposomes. This PEG-modified liposome system has potential of mucus-penetrating and provides a strategy for local treatment of gastric mucosal intestinal metaplasia.

An effective method for preventing cholestatic liver injury of Aucklandiae Radix and Vladimiriae Radix: Inflammation suppression and regulate the expression of bile acid receptors.

ETHNOPHARMACOLOGICAL RELEVANCE: Aucklandiae Radix (AR) and Vladimiriae Radix (VR) were used to treat gastrointestinal, liver and gallbladder diseases at practice. In most conditions, VR was used to be a substitute of AR or a local habit may attribute to the same main active ingredients Costunolide and Dehydrocostus lactone, which presented many similar pharmacological activities. However, other different lactone compounds in AR and VR also play a role in disease treatment, so the difference in therapeutic effects of AR and VR in related diseases needs to be further studied. AIMS OF THE STUDY: Revealing the differences between the chemical compounds of the total lactone extracts of AR and VR (TLE of AR and VR) and the differences in the protective effects of cholestatic liver injury to ensure rational use of AR and VR. STUDY DESIGN AND METHODS: The macroporous adsorption resin was used to purify and enrich the lactone compounds to obtain the total lactone extracts of AR and VR. HPLC-PDA was used to obtain the data to establish chemical fingerprint and chemometric analysis to compare similarities and differences between TLE of AR and VR. The pharmacodynamic experiment revealed how TLE of AR and VR to show protect effects on cholestatic liver injury. RESULTS: Similarity analysis results showed TLE of AR and VR had a high similarity (>0.9). Nevertheless, difference analysis results showed 4 compounds, Costunolide, Dehydrocostus lactone, 3ß-acetoxy-11ß-guaia-4 (15), 10 (14)-diene-12,6α-olide and vladinol F may contribute to the differences between them. The pharmacodynamics experiments results showed the TLE of AR and VR affected the different liver cholate-associated transporters mRNA expression (TLE of AR up-regulated CYP7A1, TLE of VR down-regulated FXR and BSEP), the TLE of AR and VR had an effect to regulate biochemical indicators (AST, ALT, ALP, TBA) of liver function, and TLE of VR was better than TLE of AR in reducing the expression of inflammatory factors (IL-6 and IL-1ß). CONCLUSION: The liver protection of AR and VR have been confirmed, but the differences of material basis and mechanism of drug efficacy needed further study to guarantee formulation research and provide theoretical references for clinical rational applications of AR and VR.

Aucklandiae Radix and Vladimiriae Radix: A systematic review in ethnopharmacology, phytochemistry and pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Aucklandiae Radix (AR) and Vladimiriae Radix (VR), as commonly used traditional Chinese herbal medicine, were widely used in the treatment of gastrointestinal diseases. The two herbal medicines were warm, pungent and bitter. They entered the spleen, stomach, large intestine and gallbladder meridians, and had the effect of promoting qi circulation to relieve pain. It is usually used for chest and hypochondrium, abdominal fullness and pain, tenesmus, indigestion, and warming the middle to harmonize the stomach in clinically. AIM OF THIS REVIEW: To provide a reference for the identification of traditional use, the material basis of efficacy and preclinical research between AR and VR, this review systematically summarized the similarities and differences in ethnopharmacology, phytochemistry and modern pharmacology. MATERIALS AND METHODS: The literature information was collected systematically from the electronic scientific databases, including PubMed, Science Direct, Google Scholar, Web of Science, Geen Medical, China National Knowledge Infrastructure, as well as other literature sources, such as classic books of herbal medicine, master's thesis, doctoral thesis. RESULTS: In the plateau areas of Sichuan Province, VR used to be regarded as substitute or local habit for AR, which is regularly used for chest, abdominal fullness and pain, diarrhea, and other related diseases. In Chinese Pharmacopoeia (ChP) 2020 edition, 145 prescription preparations with AR were collected, such as Xianglian Wan, Muxiang Shunqi Wan, Liuwei Muxiang San. However, only one prescription preparation (Jiuxiang Zhitong Wan) contained VR. Additionally, 237 and 254 chemical components were separately isolated and identified from AR and VR, 69 kinds of compounds were common among them, and the significant differences were presented in sesquiterpene lactones, monoterpenoids, triterpenoids and phenylpropanoids. Moreover, Costunolide (COS) and Dehydrocostus lactone (DEH), two main research objects of modern pharmacology, showed multiple pharmacological activities. Not only could they inhibit the activity of some cancer cells (such as breast cancer and leukemia cells), but they regulated the levels of various inflammatory factors (including TNF-α, NF-κB, IL-1ß, IL-6) and repressed the growth and reproduction of various microorganisms (like Helicobacter pylori, Staphylococcus aureus). CONCLUSION: COS and DEH as the common active components, provide a certain basis for local medicine about the substitution of VR for AR in Sichuan province of China in the past. In addition, the sesquiterpenoids are the main common compounds in AR and VR by collecting and collating a large number of literature and various data websites. Furthermore, AR and VR have significant differences in ethnopharmacology and phytochemistry, especially in sesquiterpene lactones, monoterpenoids, triterpenoids and phenylpropanoids, and are probably viewed as reference of a separate list of AR and VR in Chinese Pharmacopoeia.

Study of the therapeutic effect of raw and processed Vladimiriae Radix on ulcerative colitis based on intestinal flora, metabolomics and tissue distribution analysis.

BACKGROUND: The intestinal flora imbalance and metabolic disorders are closely related to the pathogenesis of ulcerative colitis (UC). As a commonly used herb for the treatment of gastrointestinal diseases, Vladimiriae Radix (VR) has been used for hundreds of years, and its main active ingredients are costunolide (COS) and dehydrocostus lactone (DEH). Clinical usage habits and previous studies have shown that the processed Vladimiriae Radix (pVR) seems to be more suitable for treating bowel disease than the raw Vladimiriae Radix (rVR), but there is still no relevant comparative study. PURPOSE: To investigate the therapeutic effect of rVR and pVR on UC by analyzing the intestinal flora, metabolomics and tissue distribution. METHODS: UC rat models were established to investigate the anti-inflammatory activities of rVR and pVR by enzyme-linked immunosorbent assay (ELISA), and to study their regulation of intestinal flora and metabolism by 16s rRNA gene analysis and Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS). Moreover, the distribution of COS and DEH in UC mouse tissues were also observed by High Performance Liquid Chromatography Mass Spectrometry (HPLC-MS). RESULTS: rVR and pVR reduced tissue damage and the levels of TNF-α, IL-6, IL-1ß, IL-10, TGF-ß and MPO, especially pVR. 16s rRNA gene analysis showed that rVR superior in ameliorating species evenness and restoring the abundance of Lachnospiraceae and Ruminococcaceae, while pVR is better at increasing the richness and the abundance of Prevotellaceae. Metabolomics analysis suggested that rVR regulates the ß-alanine, pantothenic acid and coenzyme A biosynthesis, but pVR regulates more abundant metabolic pathways. The tissue distribution data indicated the accumulation of COS and DEH in the gastrointestinal tract. CONCLUSION: rVR and pVR had obvious therapeutic effect on UC. The potential mechanisms might be regulating abnormal metabolism, affecting the diversity and structure of intestinal flora, and accumulation of COS and DEH in colon.

Shikonin promotes ubiquitination and degradation of cIAP1/2-mediated apoptosis and necrosis in triple negative breast cancer cells.

BACKGROUND: Shikonin (SKO) is a natural naphthoquinone derived from Chinese herbal medicine Arnebiae Radix with high development potentials due to its anti-inflammatory and anti-tumor activities. Overwhelming evidences have indicated that SKO can induce both necrosis and apoptosis in cancer cells, while the mechanisms for triple negative breast cancer cells is still need to be disclosed. METHODS: In this study, kinds of molecular biological technologies, including flow-cytometry, Western blot, immunoprecipitation, enzyme-linked immunosorbent assay (ELISA) as well as real-time quantitative PCR (RT-qPCR), were applied for investigation on the underlying mechanisms of SKO induced necrosis and apoptosis for MDA-MB-231 cells. Inhibitors were also used for validation ofthe key signaling pathways involved in SKO triggered necrosis and apoptosis. RESULTS: We found that SKO significantly triggered necrosis and apoptosis of MDA-MB-231 cells in both a concentration- and time-dependent manner. Mechanism studies demonstrated that SKO significantly promoted the autoubiquitination levels and facilitated the proteasome dependent degradation of cellular inhibitor of apoptosis protein 1 (cIAP1) and cIAP2 in MDA-MB-231 cells. Autoubiquitination and degradation of cIAP1 and cIAP2 induced by SKO further led to significant decreased ubiquitination and inactivation of RIP1, which played an important role in inhibition of pro-survival and accelerating of necrosis of MDA-MB-231 cells. Treatment with proteasome inhibitor lactacystin significantly rescued the cell viability induced by treatment of SKO. CONCLUSIONS: Our results demonstrate that SKO promotes the autoubiquitination and degradation of cIAP1 and cIAP2, which further induces the decrease of the ubiquitination of RIP1 to inhibit the activation of pro-survival signaling pathways and accelerate the necrosis of MDA-MB-231 cells. The disclosed mechanisms of SKO induced necrosis and apoptosis in our study is firstly reported, and it is believed that SKO could be considered as a potential candidate and further developed for the treatment of triple negative breast cancer.

Comparative study of raw and processed Vladimiriae Radix on pharmacokinetic and anti-acute gastritis effect through anti-oxidation and anti-inflammation.

BACKGROUND: Vladimiriae Radix (VR) is the dry root of Vladimiria souliei (Franch.) Ling or Vladimiria souliei (Franch.) Ling var. cinerea Ling. Costunolide (CO) and dehydrocostus lactone (DE) are the two most effective active ingredients of VR. Raw Vladimiriae radix (rVR) and processed Vladimiriae radix (pVR) are the two most common forms. They have been used for hundreds of years to treat gastritis, gastric ulcer and gastrointestinal pain, but their protective effects on gastric mucosa have been widely considered to be different, and the mechanism is not clear. PURPOSE: A comparative study of in vivo process and efficacy difference of raw and processed Vladimiriae Radix was carried out to explore the treatment mechanism and to provide reference for the rationality of clinical usage. METHODS: In this study, multi-batch rVR and pVR were used to establish the characteristic chromatograms through high performance liquid chromatography (HPLC) to control the qualities of their extracts. A rapid and accurate ultra-high performance liquid chromatography - mass spectrometry (UPLC-MS) method was established and verified, and the concentrations of CO and DE in plasma of rats after oral administration were determined to analyze the pharmacokinetics. The anti-inflammatory and antioxidant activities of ethanol-induced acute gastric mucosa injury (AGMI) in rats were quantitatively analyzed by ELISA and Westernblot methods. RESULTS: Characteristic chromatograms study showed that there were 9 common characteristic peaks between the chromatograms of rVR and pVR, and there was a high level (> 0.90) of the similarity between batches (only one batch less than 0.90). The increased levels of Tmax, T1/2 and MRT were found in rats treated with the pVR. Animal model studies indicated that both the two forms of VR could relieve AGMI, but pVR could more effectively reduce the content of ethanol in blood and lower the levels of TNF-α, IL-6, IL-1ß, NO, iNOS and MDA, and increase the level of SOD. Results of Westernblot proved that pVR also could inhibit the expression of NF-κB p65, IκBα and up-regulate the expression of HO-1 and NRF2 more operatively to protect gastric mucosa through anti-inflammatory and antioxidant stress mechanisms. CONCLUSION: Compared with rVR, pVR has an accelerated absorption in vivo and its effect time was prolonged, and the observed improvement of anti-AGMI effect was achieved through anti-oxidation and anti-inflammation regulation.

Analysis of the similarities and differences between Auclandia and Vladimirae rhizomes by chemical profiling and chemometric analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Aucklandiae Radix (AR) and Vladimiriae Radix (VR), as traditional Chinese medicine, have been included in many editions of Chinese Pharmacopoeia with similar efficacy such as promoting qi and relieving pain, which are used to treat chest, hypochondriac, abdominal fullness and pain, diarrhea and tenesmus. In most conditions, VR is used to be a substitute of AR or a local habit. However, whether VR could substitute for AR to play a same role in the formulation and clinical applications needs further study. AIM OF THE STUDY: In this study, similarities and differences between AR and VR would be assessed, and possible reasons that may influence the efficacy of the AR and VR would be explained from the perspective of chemical composition. MATERIALS AND METHODS: HPLC-PDA was used to obtain the data of 10 batches of AR and VR, and to establish chemical fingerprint and chemometric analysis. UPLC-ESI-Q-TOF-MS was used to identify the structure of chemical compounds which contributed to the differences between AR and VR. RESULTS: The chemical fingerprint analysis results showed that 20 peaks in common for AR and 26 peaks in common for VR both presented a good similarity (>0.9), and 15 peaks in common for AR and VR also showed a good similarity (>0.9). Nevertheless, chemometric showed AR was distinct from VR and three chemical compounds, which leading to their differences, were identified by UPLC-ESI-Q-TOF-MS. The three chemical compounds were 3ß-acetoxy-11ß-guaia-4 (15),10 (14)-diene-12,6α-olide, 10α,14-epoxy-11ß-guaia-4 (15)-ene-12,6α-olide and costunolide, respectively. CONCLUSION: In general, AR and VR were highly similar, but their differences were deserved to be paid attention to. This research could provide reference for quality control and set a foundation for clinical applications of AR and VR.

Mechanistic evaluation of gastro-protective effects of KangFuXinYe on indomethacin-induced gastric damage in rats.

KangFuXinYe (KFX), the ethanol extract of the dried whole body of Periplaneta americana, is a well-known important Chinese medicine preparation that has been used to treat digestive diseases such as gastric ulcers for many years in China. However, its therapeutic effect and mechanism are not yet well understood. Thus, the aim of this study was to investigate the gastro-protective effects of KangFuXinYe (KFX) in indomethacin-induced gastric damage. Rats were randomly divided into six groups as follows: control, treated with indomethacin (35 mg·kg-1), different dosages of KFX (2.57, 5.14 and 10.28 mL·kg-1, respectively) plus indomethacin, and sucralfate (1.71 mL·kg-1) plus indomethacin. After treatment, rat serum, stomach and gastric homogenates were collected for biochemical tests and examination of histopathology firstly. Rat serum was further used for metabolomics analysis to research possible mechanisms. Our results showed that KFX treatment alleviated indomethacin-induced histopathologic damage in rat gastric mucosa. Meanwhile, its treatment significantly increased cyclooxygenase-1 (COX-1), prostaglandin E2 (PGE2) and epidermal growth factor (EGF) levels in rat serum and gastric mucosa. Moreover, KFX decreased cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6) levels. Nine metabolites were identified which intensities significantly changed in gastric damage rats, including 5-hydroxyindoleacetic acid, indoxylsulfuric acid, indolelactic acid, 4-hydroxyindole, pantothenic acid, isobutyryl carnitine, 3-methyl-2-oxovaleric acid, sphingosine 1-phosphate, and indometacin. These metabolic deviations came to closer to normal levels after KFX intervention. The results indicate that KFX (10.28 mL·kg-1) exerts protective effects on indomethacin-induced gastric damage by possible mechanisms of action (regulating tryptophan metabolism, protecting the mitochondria, and adjusting lipid metabolism, and reducing excessive indomethacin).

Quality assessment and differentiation of Aucklandiae Radix and Vladimiriae Radix based on GC-MS fingerprint and chemometrics analysis: basis for clinical application.

Vladimiriae Radix, a geo-authentic medicinal herb found in Sichuan Province in China, is highly similar in chemical composition and pharmacological activity to Aucklandiae Radix. It is often used in local practice and as a substitute for Aucklandiae Radix in the treatment of gastrointestinal tract diseases. However, Vladimiriae Radix is preferred to Aucklandiae Radix in traditional Chinese medicine in Sichuan. In order to compare the difference in quality between the two species and differentiate them according to their chemical profiles, and further to explain the rationality of using Vladimiriae Radix as a substitute and explore the reason for the medication preference in Sichuan, similarity was evaluated using gas chromatography-mass spectrometry (GC-MS) fingerprinting and chemometric analysis. Volatile compounds were identified by comparing mass spectra with spectral data from the National Institute of Standards and Technology library 14.L (NIST 14.L) and the linear retention indices (RI) with those previously reported. The results showed that the similarity between the samples from Aucklandiae Radix (>96%) was greater than that of Vladimiriae Radix (>80%). In addition, 41 and 38 compounds were identified in 10 batches of Vladimiriae Radix and Aucklandiae Radix, respectively, and 21 compounds were common to both species, of which dehydrocostus lactone and aplotaxene were abundant in both. However, γ-patchoulene, longicyclene, ß-gurjunene, humulene1,2-epoxide, and ß-patchoulene were unique to Vladimiriae Radix, while 4-terpineol, α-ionone, trans-α-bergamotene, γ-selinene, and camphene were characteristic compounds of Aucklandiae Radix. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) suggested that the two species were well differentiated with regard to the level of essential oils. Orthogonal partial least squares discriminant analysis (OPLS-DA) further showed that compounds including costol, aplotaxene, caryophyllene, humulene, and ß-eudesmol, together with the characteristic compounds of the two species, could be regarded as potential markers for differentiation, among which ß-eudesmol, which is richer in Vladimiriae Radix, and ß-patchoulene, which is unique to Vladimiriae Radix, have potential therapeutic effects on gastrointestinal diseases. The results obtained in this study distinguished Vladimiriae Radix and Aucklandiae Radix on a chemical level, and the similarity in chemical constituents may provide a basis for the rationality of Vladimiriae Radix as a substitute, while ß-patchoulene and ß-eudesmol existing in Vladimiriae Radix provide a theoretical basis for its preferential use in Sichuan. The analysis method established here has important implications for the quality control and differentiation of Vladimiriae Radix and Aucklandiae Radix, which can also serve as a reference for the identification of similar species. Graphical abstract.

Purified Phlorizin from DocynIa Indica (Wall.) Decne by HSCCC, Compared with Whole Extract, Phlorizin and Non-Phlorizin Fragment Ameliorate Obesity, Insulin Resistance, and Improves Intestinal Barrier Function in High-Fat-Diet-Fed Mice.

Natural products generally contain complex and multiple bioactive compounds that are responsible for the effects on health through complicated synergistic and/or suppressive actions. As an important raw material of local ethnic minority tea, ethnomedicines and food supplements in southwestern areas of China, Docynia indica (Wall.) Decne (DID) mainly consists of phlorizin (PHZ), which is the main active component. In this study, the holistic activities and the interactions of components of PHZ, non-phlorizin (NP) in the DID extract (DIDE) were evaluated. A rapid and effective high-speed counter-current chromatography (HSCCC) was performed to knock out PHZ from DIDE and the purity of PHZ was 96.01% determined by HPLC, with a recovery rate of 96.76%. After 13 weeks of treatment course in a high-fat diet (HFD)-induced obese mice model, the results revealed that the DIDE and PHZ significantly decreased weight gain, blood lipid levels, hyperplasia of adipocytes and alleviated inflammation (p < 0.05). Both DIDE and PHZ improves insulin resistance (p < 0.001). Meanwhile, the intestinal barrier function was improved compared to HFD group, through the determination of serum lipopolysaccharides (LPS), glucagon-likepeptide-2 (GLP-2) and hematoxylin-eosin staining of jejunum. Interestingly, after NP treatment, the metabolic syndrome of the HFD-induced obesity appeared to have a similar improvement. All the experiments showed that there is a synergistic weakening phenomenon when PHZ and NP interact with each other in the mixed state. In conclusion, for the PHZ and NP showing a good effect on anti-obesity, anti-inflammation, and intestinal barrier function, DIDE could be a good source of functional food to prevent obesity.

Chemical Fingerprint and Quantitative Analysis for the Quality Evaluation of Docynia dcne Leaves by High-Performance Liquid Chromatography Coupled with Chemometrics Analysis.

Docynia dcne leaf from the genus of Docynia Dcne (including three species of Docynia delavayi, Docynia indica and Docynia longiunguis.) is an important raw material of local ethnic minority tea, ethnomedicines and food supplements in southwestern areas of China. However, D. dcne leaves from these three species are usually used confusingly, which could influence the therapeutic effect of it. A rapid and effective method for the chemical fingerprint and quantitative analysis to evaluate the quality of D. dcne leaves was established. The chemometric methods, including similarity analysis, hierarchical cluster analysis and partial least-squares discrimination analysis, were applied to distinguish 30 batches of D. dcne leaf samples from these three species. The above results could validate each other and successfully group these samples into three categories which were closely related to the species of D. dcne leaves. Moreover, isoquercitrin and phlorizin were screened as the chemical markers to evaluate the quality of D. dcne leaves from different species. And the contents of isoquercitrin and phlorizin varied remarkably in these samples, with ranges of 6.41-38.84 and 95.73-217.76 mg/g, respectively. All the results indicated that an integration method of chemical fingerprint couple with chemometrics analysis and quantitative assessment was a powerful and beneficial tool for quality control of D. dcne leaves, and could be applied also for differentiation and quality control of other herbal preparations.

[Research status of Periplaneta americana with analyses and prospects of key issues].

Periplaneta americana is one of the common traditional Chinese medicines, which has a long application history. It can tonify spleen, promote blood circulation, induce diuresis to alleviate edema, and promote granulation. It is clinically used for the treatment of alimentary canal diseases, chronic heart failure, cutaneous lesion, periodontitis and other diseases. There are some representative prescriptions, such as Kangfu Xinye, Xinmailong injection, Ganlong capsule, and Xiaozheng Yigan tablet. This paper reviewed the chemical components, pharmacological effects and clinical applications of P. americana, firstly summarized standards for the quality control of P. americana, found out and analyzed the key problems in the research. The aim of this paper is to provide the references for the further development and application of P. americana.

In Vitro and In Vivo Antioxidant Activities of the Flowers and Leaves from Paeonia rockii and Identification of Their Antioxidant Constituents by UHPLC-ESI-HRMSn via Pre-Column DPPH Reaction.

The genus Paeonia, also known as the "King of Flowers" in China, is an important source of traditional Chinese medicine (TCM). Plants of this genus have been used to treat a range of cardiovascular and gynecological diseases. However, the potential pharmacological activity of one particular species, Paeonia rockii, has not been fully investigated. In the first part of the present study, 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) acid (ABTS), reducing power assays, and metal ion chelating assays were used to investigate the in vitro antioxidant activities of Paeonia rockii. In the second portion of the study, a mouse model of d-galactose-induced aging was used to validate the antioxidant effects of the flowers from Paeonia rockii in vivo. Lastly, potential antioxidant constituents were screened and identified by ultra-high pressure liquid chromatography and electrospray ionization coupled with high-resolution mass spectrometry (UHPLC-ESI-HRMSn) combined with the DPPH assay. Results indicated that the flowers and leaves exhibited stronger antioxidant activity than ascorbic acid in vitro. The therapeutic effect of Paeoniarockii was determined in relation to the levels of biochemical indicators, such as 8-iso-prostaglandin F2α (8-iso PGF2α) in the serum, superoxide dismutase (SOD), protein carbonyl, malondialdehyde (MDA), and glutathione (GSH) in the liver and brain, after daily intra-gastric administration of different concentrations of extracts (100, 200 and 400 mg/kg) for three weeks. The levels of 8-iso PGF2α (p < 0.01) and protein carbonyl groups (p < 0.01) were significantly reduced, whereas those of SOD (p < 0.05) had significantly increased, indicating that components of the flowers of Paeonia rockii had favorable antioxidant activities in vivo. Furthermore, UHPLC-ESI-HRMSn, combined with pre-column DPPH reaction, detected 25 potential antioxidant compounds. Of these, 18 compounds were tentatively identified, including 11 flavonoids, four phenolic acids, two tannins, and one monoterpene glycoside. This study concluded that the leaves and flowers from Paeonia rockii possess excellent antioxidant properties, highlighting their candidacy as "new" antioxidants, which can be utilized therapeutically to protect the body from diseases caused by oxidative stress.

Effect of Chemical Profiling Change of Processed Magnolia officinalis on the Pharmacokinetic Profiling of Honokiol and Magnolol in Rats.

The stem of Magnoliae officinalis (MO) cortex is always preliminarily processed before being applied in traditional Chinese medicine. The definite bioavailability of honokiol (HO) and magnolol (MA) in processed MO (PMO) and the effect of chemical profiling change on the pharmacokinetics of HO and MA are always a greater challenge compared with those of MO. Compared with that of MO, the pharmacokinetic profiling of HO and MA in the PMO was significantly changed and the mean Tmax of HO and MA was increased by 31 and 50% (P < 0.05), respectively; the mean AUC0-t and Cmax of HO were increased by 36 and 24% (P < 0.05), respectively. Subsequently, the chemical profiling of MO and PMO was investigated by a simple and rapid LC-Q/TOF-MS coupled with multivariate analysis method. Principal component analysis and hierarchical cluster analysis of the chromatographic data demonstrated that the chemical profiling of PMO was significantly different from that of MO. Eight marker components including six alkaloids (magnocurarine, magnoflorine, roemerine and three unidentified peaks) and two lignans (obovatol and MA) were screened out by partial least-squares discriminant analysis. The results indicated that the changes of eight marker components of PMO may have an effect on the pharmacokinetic profiles of HO and MA.

Rapid isolation and purification of phorbol esters from Jatropha curcas by high-speed countercurrent chromatography.

In this work, a high-speed countercurrent chromatography (HSCCC) method was established for the preparation of phorbol esters (PEs) from Jatropha curcas. n-Hexane-ethyl acetate-methanol-water (1.5:1.5:1.2:0.5, v/v) was selected as the optimum two-phase solvent system to separate and purify jatropha factor C1 (JC1) with a purity of 85.2%, as determined by HPLC, and to obtain a mixture containing four or five PEs. Subsequently, continuous semipreparative HPLC was applied to further purify JC1 (99.8% as determined by HPLC). In addition, UPLC-PDA and UPLC-MS were established and successfully used to evaluate the isolated JC1 and PE-rich crude extract. The purity of JC1 was only 87.8% by UPLC-UV. A peak (a compound highly similar to JC1) was indentified as the isomer of JC1 by comparing the characteristic UV absorption and MS spectra. Meanwhile, this strategy was also applied to analyze the PE-rich crude extract from J. curcas. It is interesting that there may be more than 15 PEs according to the same quasi-molecular ion peaks, highly similar sequence-specific fragment ions, and similar UV absorption spectrum.

Chemical Profiling Assisted Quality Assessment of Gentianae macrophyllae by High-Performance Liquid Chromatography Using a Fused-Core Column.

A fast and sensitive HPLC coupled with multivariate analysis was utilized to assist the quality assessment of Gentianae macrophyllae radix (Qinjiao). Seventy-six peaks were separated and detected on a fused-core column with 35 min. Principal component analysis and hierarchical cluster analysis of the chromatographic data showed that the 17 batches of Qinjiao could be well categorized into three groups, which were closely related to the origins of them. Partial least square-discriminant analysis (PLS-DA) exhibited that the quality differentiation might be explained by at least four components, in which, gentiopicroside (GE), loganic acid (LA), swertiamarin (SA) were characterized by external reference, one of them was unidentified in this work. The content levels of GE, LA and SA were more relevant to comprehensive quality of Qinjiao than the ones of shanzhiside methyl ester and sweroside was confirmed by the PLS prediction models through analyzing the relevance of the chemical profiling to the levels of them. The present study not only indicated that GE, LA, SA and one unidentified compound were the rational markers to represent the comprehensive quality of Qinjiao but also demonstrated the power of chemical profiling platform in the quality assessment of Chinese medicine herbals.