Spectrum-Effect Relationship in Chinese Herbal Medicine: Current Status and Future Perspectives.

The quality of Chinese herbal medicine (CHM) directly impacts clinical efficacy and safety. Fingerprint technology is an internationally recognized method for evaluating the quality of CHM. However, the existing quality evaluation models based on fingerprint technology have blocked the ability to assess the internal quality of CHM and cannot comprehensively reflect the correlation between pharmacodynamic information and active constituents. Through mathematical methods, a connection between the "Spectrum" (fingerprint) and the "Effect" (pharmacodynamic data) was established to conduct a spectrum-effect relationship (SER) of CHM to unravel the active component information associated with the pharmacodynamic activity. Consequently, SER can efficiently address the limitations of the segmentation of chemical components and pharmacodynamic effect in CHM and further improve the quality evaluation of CHM. This review focuses on the recent research progress of SER in the field of CHM, including the establishment of fingerprint, the selection of data analysis methods, and their recent applications in the field of CHM. Various advanced fingerprint techniques are introduced, followed by the data analysis methods used in recent years are summarized. Finally, the applications of SER based on different research subjects are described in detail. In addition, the advantages of combining SER with other data are discussed through practical applications, and the research on SER is summarized and prospected. This review proves the validity and development potential of the SER and provides a reference for the development and application of quality evaluation methods for CHM.

Kaempferol Alleviates Murine Experimental Colitis by Restoring Gut Microbiota and Inhibiting the LPS-TLR4-NF-κB Axis.

Intestinal microbiota dysbiosis is an established characteristic of ulcerative colitis (UC). Regulating the gut microbiota is an attractive alternative UC treatment strategy, considering the potential adverse effects of synthetic drugs used to treat UC. Kaempferol (Kae) is an anti-inflammatory and antioxidant flavonoid derived from a variety of medicinal plants. In this study, we determined the efficacy and mechanism of action of Kae as an anti-UC agent in dextran sulfate sodium (DSS)-induced colitis mice. DSS challenge in a mouse model of UC led to weight loss, diarrhea accompanied by mucous and blood, histological abnormalities, and shortening of the colon, all of which were significantly alleviated by pretreatment with Kae. In addition, intestinal permeability was shown to improve using fluorescein isothiocyanate (FITC)-dextran administration. DSS-induced destruction of the intestinal barrier was also significantly prevented by Kae administration via increases in the levels of ZO-1, occludin, and claudin-1. Furthermore, Kae pretreatment decreased the levels of IL-1ß, IL-6, and TNF-α and downregulated transcription of an array of inflammatory signaling molecules, while it increased IL-10 mRNA expression. Notably, Kae reshaped the intestinal microbiome by elevating the Firmicutes to Bacteroidetes ratio; increasing the linear discriminant analysis scores of beneficial bacteria, such as Prevotellaceae and Ruminococcaceae; and reducing the richness of Proteobacteria in DSS-challenged mice. There was also an evident shift in the profile of fecal metabolites in the Kae treatment group. Serum LPS levels and downstream TLR4-NF-κB signaling were downregulated by Kae supplementation. Moreover, fecal microbiota transplantation from Kae-treated mice to the DSS-induced mice confirmed the effects of Kae on modulating the gut microbiota to alleviate UC. Therefore, Kae may exert protective effects against colitis mice through regulating the gut microbiota and TLR4-related signaling pathways. This study demonstrates the anti-UC effects of Kae and its potential therapeutic mechanisms, and offers novel insights into the prevention of inflammatory diseases using natural products.

[Effect of application at Shu-Mu acupoint on serum uric acid in hyperuricemic rats].

OBJECTIVE: To observe the effect of application at Back-Shu with Front-Mu acupoints on serum uric acid (SUA) and kidney uric acid transport related proteins in hyperuricemia rats, so as to explore the mechanism of Shu-Mu acupoint application on treatment of hyperuricemia. METHODS: SD rats were randomly divided into blank control, model, vaseline application and medication application groups, with 8 rats in each group. The hyperuricemia rat model was established by gavage of potassium oxonate. Rats in the vaseline application group received application of vaseline at bilateral "Ganshu"(BL18) and "Qimen"(LI14), "Pishu"(BL20) and "Zhangmen"(LR13), "Shenshu" (BL23) and "Jingmen"(GB25). Rats in the medication application group received application of traditional Chinese medicine at the same acupoints. The contents of SUA and creatinine (SCr) were detected by automatic biochemical analyzer. H.E. staining was used to observe the pathological changes of kidney. And the protein expression levels of organic anion transporter 1(OAT1) and adenosine triphosphate binding cassette transporter G2(ABCG2) were detected by immunohistochemistry. RESULTS: Rats in the model group showed symptoms such as polydipsia, polyuria, loose stools, fatigue, weakness, etc. The renal tubules atrophied, and urate crystals can be seen in the lumen. Compared with the control group. the SUA content in the model group increased (P<0.01)and the expressions of OAT1 and ABCG2 protein in kidney decreased (P<0.01). After intervention and in comparison with the model group showed that, the diet, excretion function, and mental state of the rats in the medication application group returned to normal, and the pathological changes of the kidney tissue were alleviated, the SUA content was down-regulated(P<0.01)and the expression levels of OAT1 and ABCG2 in the kidney up-regulated (P<0.01). There was no statistically significant difference in the SCr content among the 4 groups (P＞0.05). CONCLUSION: Medication application at Shu-Mu points can effectively reduce the SUA level of hyperuricemia rats, which may be related to its effects in up-regulating the protein expressions of OAT1 and ABCG2 in the kidney and reducing the damage to the kidneys.

[Location of acupoint Xuanzhong(GB39)].

For a long time, there have been many opinions about the location of Xuanzhong(GB39) point in the academic field. The author analyzed the location of GB39 in the main acupuncture literature in ancient times, textbooks of universities and colleges of traditional Chinese medicine after the founding of the People's Republic of China, national standards and more influential acupuncture works. From ancient times to the evolution of the location of the point, it is believed that the point should be located 3 cun above the lateral malleolus, between the tibial anterior ridge and the anterior edge of the fibula.

Projecting neurons in spinal dorsal horn send collateral projections to dorsal midline/intralaminar thalamic complex and parabrachial nucleus.

Itch is an annoying sensation that always triggers scratching behavior, yet little is known about its transmission pathway in the central nervous system. Parabrachial nucleus (PBN), an essential transmission nucleus in the brainstem, has been proved to be the first relay station in itch sensation. Meanwhile, dorsal midline/intralaminar thalamic complex (dMITC) is proved to be activated with nociceptive stimuli. However, whether the PBN-projecting neurons in spinal dorsal horn (SDH) send collateral projections to dMITC, and whether these projections involve in itch remain unknown. In the present study, a double retrograde tracing method was applied when the tetramethylrhodamine-dextran (TMR) was injected into the dMITC and Fluoro-gold (FG) was injected into the PBN, respectively. Immunofluorescent staining for NeuN, substance P receptor (SPR), substance P (SP), or FOS induced by itch or pain stimulations with TMR and FG were conducted to provide morphological evidence. The results revealed that TMR/FG double-labeled neurons could be predominately observed in superficial laminae and lateral spinal nucleus (LSN) of SDH; Meanwhile, most of the collateral projection neurons expressed SPR and some of them expressed FOS in acute itch model induced by histamine. The present results implicated that some of the SPR-expressing neurons in SDH send collateral projections to the dMITC and PBN in itch transmission, which might be involved in itch related complex affective/emotional processing to the higher brain centers.

Traceability of wild Paris polyphylla Smith var. yunnanensis based on data fusion strategy of FT-MIR and UV-Vis combined with SVM and random forest.

Paris polyphylla Smith var. yunnanensis (Franch.) Hand.-Mazz (PPY) was a frequently used herbal medicine in pharmaceutical field and different provenances might affect the clinical efficacy. Tracing the geographical origin was an important portion for PPY authentication and quality assessment. Present study was compared low-, mid- and high-level data fusion methodology for geographical traceability of PPY samples (161 batches) combined with multivariate classification methods such as support vector machine gird search (SVM-GS) and random forest (RF) on the basis of Fourier transform mid-infrared (FT-MIR) and ultraviolet-visible (UV-Vis) spectra. Compared with the low- and mid-level data fusion strategy results basing on SVM-GS algorithm, result of high-level data fusion method (calculated by RF) was more satisfying. Result of RF basing on high-level data fusion strategy showed that merely two samples were misclassified and one sample was multiple assigned after voting with fuzzy set theory. Values of specificity, sensitivity, and accuracy rates were exceeded 0.91, 0.99 and 90.91%, for each class respectively, satisfying results of these were shown in training and test sets for high-level data fusion method. This feasible result indicated that the RF algorithm could establish a reliable and good performance model in geographical traceability on the basis of high-level data fusion strategy. Combination of high-level data fusion and RF algorithm could consider as a good choice for establishing a discrimination multivariate model for origins identification of PPY samples.

Neuroprotection of tanshinone IIA against cerebral ischemia/reperfusion injury through inhibition of macrophage migration inhibitory factor in rats.

BACKGROUND: Ischemia/reperfusion (I/R) injury is associated with systemic inflammatory response. Macrophage migration inhibitory factor (MIF) has been implicated in many inflammatory processes. Tanshinone IIA (TSA) is one of the active ingredients in danshen, which derived from the dried root or rhizome of Salviae miltiorrhizae Bge. Recent studies have demonstrated that TSA has protective effects against focal cerebral I/R injury. However, little is known about the underlying mechanisms. Here we put forward the hypothesis that TSA acts through inhibition of MIF expression during focal cerebral I/R injury in rats. METHODOLOGY/PRINCIPAL FINDINGS: Rats were subjected to middle cerebral artery occlusion (MCAO) for 2 hours. This was followed by reperfusion. We measured neurological deficits, brain water content, and infarct volume, and found that neurological dysfunction, brain edema, and brain infarction were significantly attenuated by TSA 6 hours after reperfusion. We also measured myeloperoxidase (MPO) activity at 6 and 24 hours, and found that neutrophil infiltration was significantly higher in the vehicle+I/R group than in the TSA+I/R group. ELISA demonstrated that TSA could inhibit MIF expression and the release of TNF-α and IL-6 induced by I/R injury. Western blot analysis and immunofluorescence staining showed that MIF expression was significantly lower in the TSA+I/R group than in the vehicle+I/R group. MIF was found almost all located in neurons and hardly any located in astrocytes in the cerebral cortex. Western blot analysis and EMSA demonstrated that NF-κB expression and activity were significantly increased in the vehicle+I/R group. However, these changes were attenuated by TSA. CONCLUSION/SIGNIFICANCE: Our results suggest that TSA helps alleviate the proinflammatory responses associated with I/R-induced injury and that this neuroprotective effect may occur through down-regulation of MIF expression in neurons.

[Effect of triptolide on reversing hypermethylation of apc gene in Jurkat cells and its possible mechanisms].

This study was aimed to investigate the effect of traditional Chinese medicine, Triptolide (TPL) on reversing hypermethylation of antioncogene (apc gene) in acute lymphoblastic leukemia cell line Jurkat in vitro and to explore its mechanisms. The effects of TPL on cell growth, proliferation and cell cycle were detected by growth curve, MTT assay, colony formation test and flow cytometry, respectively. The effect of TPL on apc gene methylation of Jurkat cells was analyzed by nested methylation specific PCR; the expressions of apc gene, dnnt3a, dnmt3b mRNA were measured by RT-PCR; the protein expression of apc gene was detected by Western blot. The results showed that as compared with untreated control cells, the TPL of different concentrations could significantly inhibit growth and proliferation of Jurkat cells in dose-and time-dependent manners with IC50 19.7 ng/ml at 48 hours. All cytosines in CpG dinucleotides in untreated Jurkat cells had no changed, while all cytosines in Jurkat cells treated with TPL had been converted to thymidine suggesting the methylation of apc gene in Jurkat cells. The TPL could reverse hypermethylation of apc gene and induced the mRNA and protein expression of apc gene in dose-dependent manner. It is concluded that the small dose of TPL can obviously suppress the proliferation of Jurkat cells, activate and up-regulate the expression of apc gene through demethylation of apc gene resulting from DNMT and/or direct action, thereby inhibit the proliferation rate of Jurkat cells.