Herb pair Danggui-Honghua has been frequently used for treatment of blood stasis syndrome (BSS) in China, one of the most common clinical pathological syndromes in traditional Chinese medicine (TCM). However, its therapeutic mechanism has not been clearly elucidated. In the present study, a feasible system pharmacology model based on chemical, pharmacokinetic and pharmacological data was developed via network construction approach to clarify the mechanisms of this herb pair. Thirty-one active ingredients of Danggui-Honghua possessing favorable pharmacokinetic profiles and biological activities were selected, interacting with 42 BSS-related targets to provide potential synergistic therapeutic actions. Systematic analysis of the constructed networks revealed that these targets such as HMOX1, NOS2, NOS3, HIF1A and PTGS2 were mainly involved in TNF signaling pathway, HIF-1 signaling pathway, estrogen signaling pathway and neurotrophin signaling pathway. The contribution index of every active ingredient also indicated six compounds, including hydroxysafflor yellow A, safflor yellow A, safflor yellow B, Z-ligustilide, ferulic acid, and Z-butylidenephthalide, as the principal components of this herb pair. These results successfully explained the polypharmcological mechanisms underlying the efficiency of Danggui-Honghua for BSS treatment, and also probed into the potential novel therapeutic strategies for BSS in TCM.

Rhubarb is one of the most ancient, commonly used and important herbs in Chinese medicine. The modern researches of rhubarb clarified the efficacies, ingredients and mechanisms in a more scientific and rigorous way. The main chemical compositions of rhubarb include anthraquinones, anthrones, stilbenes, tannins, polysaccharides etc. These compositions show extensive pharmacological activities including regulating gastrointestinal, anticancer, antimicrobial, hepatoprotective, anti-inflammatory, protecting cardiovascular, cerebrovascular and so on. This paper reviews the recent studies on the active ingredients, pharmacological effects, clinical application and functional mechanism.

The multi-drug resistance 2 knockout (Mdr2−/−) mouse is a well-established model of cholestatic cholangiopathies. Female Mdr2−/− mice develop more severe hepatobiliary damage than male Mdr2−/− mice, which is correlated with a higher proportion of taurocholate (TCA) in bile. Although estrogen has been identified as an important player in intrahepatic cholestasis, the underlying molecular mechanisms of gender-based disparity of cholestatic injury remain unclear. The long non-coding RNA H19 is an imprinted, maternally expressed and estrogen-targeted gene, which is significantly induced in human fibrotic/cirrhotic liver and bile duct ligated mouse liver. However, whether aberrant expression of H19 accounts for gender-based disparity of cholestatic injury in Mdr2−/− mice remains unknown. The current study demonstrated that H19 was markedly induced (~200-fold) in the livers of female Mdr2−/− mice at advanced stages of cholestasis (100-day-old), but not in aged-matched male Mdr2−/− mice. During the early stages of cholestasis, H19 expression was minimal. We further determined that the hepatic H19 was mainly expressed in cholangiocytes, not hepatocytes. Both TCA and estrogen significantly activated the ERK1/2 signaling pathway and induced H19 expression in cholangiocytes. Knocking down H19 not only significantly reduced TCA/estrogen-induced expression of fibrotic genes and sphingosine 1-phosphate receptor 2 (S1PR2) in cholangiocytes, but also markedly reduced cholestatic injury in female Mdr2−/− mice. Furthermore, the expression of small heterodimer partner was substantially inhibited at advanced stages of liver fibrosis, which was reversed by H19 shRNA in female Mdr2−/− mice. Similar findings were obtained in human PSC liver samples. Conclusion H19 plays a critical role in the disease progression of cholestasis and represents a key factor that causes the gender disparity of cholestatic liver injury in Mdr2−/− mice.

Osteoarthritis (OA) is the leading cause of joint pain and disability in middle-aged and elderly patients, and is characterized by progressive loss of articular cartilage that eventually leads to a complex process involving degradation of various components of the cartilage matrix, chief among them are the cartilage-specific type II collagen (CII) and aggrecan. While the loss of aggrecan is thought to be an early and reversible process, degradation of CII is considered to be irreversible and a key step in the loss of structural and functional integrity of cartilage. Among the various matrix metalloproteinases (MMPs), MMP-13 is specifically expressed in the cartilage of human OA patients and is not present in normal adult cartilage. It is the major collagenase in OA cartilage and has the highest activity against CII. However, the clinical utility of broad-spectrum MMP inhibitors developed for treatment of OA has been restricted by dose- and duration-dependent musculoskeletal side effects in humans. Consequently, selectively inhibiting the MMP-13 would seem to be an attractive therapeutic objective. This review mainly focuses on selective MMP-13 inhibitors development in terms of OA since the late 90s, in terms of synthetic compounds of low molecular mass incorporating specific zinc-binding groups, non-zinc-binding groups. In addition, dual inhibitors of MMP-13 and aggrecanase are also reviewed. Special emphasis is placed on logistic concerns for lead compound search as well as the structure-activity relationship (SAR) in this field. Through these methods, new hope is emerging for the treatment of OA through selective inhibition of MMP-13.

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Chuanxiong Rhizoma (Chuan-Xiong, CX), the dried rhizome of Ligusticum chuanxiong Hort. (Umbelliferae), is one of the most popular plant medicines in the World. Modern research indicates that organic acids, phthalides, alkaloids, polysaccharides, ceramides and cerebrosides are main components responsible for the bioactivities and properties of CX. Because of its complex constituents, multidisciplinary techniques are needed to validate the analytical methods that support CX’s use worldwide. In the past two decades, rapid development of technology has advanced many aspects of CX research. The aim of this review is to illustrate the recent advances in the chemical analysis and biological activities of CX, and to highlight new applications and challenges. Emphasis is placed on recent trends and emerging techniques.

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We report the discovery of large amounts of cold (T ∼ 10 4 K), chemically young gas in an overdensity of galaxies at redshift z ≈ 1.6 located in the Great Observatories Origins Deep Survey southern field. The gas is identified thanks to the ultra-strong Mg ii λ2800 absorption features it imprints onto the rest-frame UV spectra of galaxies in the background of the overdensity. There is no evidence that the optically thick gas is part of any massive galaxy (i.e., M star > 4 × 10 9 M ), but rather is associated with the overdensity; less massive and fainter galaxies (25.5 mag < z < 27.5 mag) have too large an impact parameter to be causing ultra-strong absorption systems, based on our knowledge of such systems. The lack of corresponding Fe ii absorption features, not detected even in co-added spectra, suggests that the gas is chemically more pristine than the interstellar medium and outflows of star-forming galaxies at similar redshift, including the galaxies of the overdensity itself, and comparable to the most metal-poor stars in the Milky Way halo. A crude estimate of the projected covering factor of the high-columndensity gas (N H 10 20 cm −2 ) based on the observed fraction of galaxies with ultra-strong absorbers is C F ≈ 0.04. A broad, continuum absorption profile extending to the red of the interstellar Mg ii absorption line by 2000 km s −1 is possibly detected in two independent co-added spectra of galaxies belonging to the overdensity, consistent with a large-scale infall motion of the gas onto the overdensity and its galaxies. Overall, these findings provide the first tentative evidence of accretion of cold, chemically young gas onto galaxies at high redshift, possibly feeding their star formation activity. We suggest the fact that the galaxies are members of a large structure, as opposed to field galaxies, might play a significant role in our ability to detect the accreting gas.