The Efficacy and Safety of Ginkgo Terpene Lactone Preparations in the Treatment of Ischemic Stroke: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Background: This meta-analysis aimed to assess the efficacy and safety of ginkgo terpene lactone preparations including ginkgo diterpene lactone meglumine injection, ginkgolide injection, and ginkgolide B injection for ischemic stroke (IS). Methods: We searched the randomized controlled trials (RCTs) with publication date earlier than 31 August 2021 in PubMed, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Journals Database (VIP), Chinese Biomedical Literature Database (CBM), Wanfang Database, Embase, and the Cochrane Library. RevMan 5.3 software was applied to analyze the data and generate the forest plot and funnel plot. Meanwhile, publication bias was also assessed by Egger's test with STATA 12 software. Results: A total of 28 RCTs were eligible for inclusion. Among them, 23 RCTs were used to evaluate the efficacy of ginkgo terpene lactone preparations as the main treatment intervention for IS. To be specific, ginkgo diterpene lactone meglumine injection was superior to control drug in improving clinical efficacy [RR = 1.18, 95% CI (1.12, 1.24), Z = 6.36, p < 0.001] and neurological function [MD = -1.42, 95% CI (-1.91, -0.93), Z = 5.66, p < 0.001]. However, the effectiveness of the ginkgolide B injection group was equivalent to that of the control group. Additionally, ginkgolide injection achieved better clinical efficacy [RR = 1.10, 95% CI (1.02, 1.18), Z = 2.36, p = 0.02], but the changes of neurological function deficit was not obviously different between two groups [MD = -0.43, 95% CI (-4.32, 3.46), Z = 0.22, p = 0.83]. Furthermore, meta-analysis of five trials on ginkgo diterpene lactone meglumine injection combined with recombinant tissue plasminogen activator (rt-PA) thrombolytic therapy for acute IS showed that combination therapy was better in improving clinical efficacy [OR = 1.91, 95% CI (1.13, 3.22), Z = 2.41, p = 0.02] and neurological function [MD = -3.31, 95% Cl (-3.64,-2.98), Z = 19.63, p < 0.001]. Importantly, no serious adverse drug reactions/adverse drug events (ADRs/ADEs) were reported. Conclusion: Ginkgo terpene lactone preparations have good therapeutic effects on patients with IS. For acute IS, ginkgo diterpene lactone meglumine injection can be used as a complementary therapy to improve the clinical efficacy of rt-PA.

Biological Ingredient Analysis of Traditional Herbal Patent Medicine Fuke Desheng Wan Using the Shotgun Metabarcoding Approach.

With the widespread use of traditional medicine around the world, the safety and efficacy of traditional herbal patent medicine have become an increasing concern to the public. However, it is difficult to supervise the authenticity of herbal materials in mixed herbal products according to the current quality standards, especially for traditional herbal patent medicine, with a distinct variance in the dosage of herbal materials. This study utilized the shotgun metabarcoding approach to analyze the biological ingredients of Fuke Desheng Wan (FKDSW), which is an effective traditional herbal product for the treatment of dysmenorrhea. Six herbal materials were collected, and a lab-made mock FKDSW sample was produced to establish a method for the authentication assessment of biological ingredients in traditional herbal patent medicine based on shotgun metabarcoding. Furthermore, four commercial FKDSW samples were collected to verify the practicality of the shotgun metabarcoding approach. Then, a total of 52.16 Gb raw data for 174 million paired-end reads was generated using the Illumina NovaSeq sequencing platform. Meanwhile, 228, 23, and 14 operational taxonomic units (OTUs) were obtained for the ITS2, matK, and rbcL regions, respectively, after bioinformatic analysis. Moreover, no differences were evident between the assembly sequences obtained via shotgun metabarcoding and their corresponding reference sequences of the same species obtained via Sanger sequencing, except for part of the ITS2 and matK assembly sequences of Paeonia lactiflora Pall., Saussurea costus (Falc.) Lipsch. and Bupleurum chinense DC. with 1-6 different bases. The identification results showed that all six prescribed ingredients were successfully detected and that the non-authentic ingredient of Bupleuri Radix (Chaihu, Bupleurum chinense DC. or Bupleurum scorzonerifolium Willd.) was found in all the commercial samples, namely Bupleurum falcatum L. Here, 25 weed species representing 16 genera of ten families were detected. Moreover, 26 fungal genera belonging to 17 families were found in both lab-made and commercial FKDSW samples. This study demonstrated that the shotgun metabarcoding approach could overcome the biased PCR amplification and authenticate the biological ingredients of traditional herbal patent medicine with a distinct variance in the dosage of the herbal materials. Therefore, this provides an appropriate evaluation method for improving the safety and efficacy of traditional herbal patent medicine.

Precise Species Detection in Traditional Herbal Patent Medicine, Qingguo Wan, Using Shotgun Metabarcoding.

As one of the high-incidence diseases in the world, pharyngitis seriously affects the lives of those with the condition. Qingguo Wan is a herbal medicine used for treating pharyngitis, and its quality evaluation is currently only accomplished via traditional identification. However, precise identification becomes challenging with fake products on the market or fungal contamination during the production process. This study used the Illumina NovaSeq platform for targeting the ITS2, psbA-trnH, matK, and rbcL sequences to survey the species composition of lab-made and commercial samples. The results showed that a total of 34.56 Gb of raw data that was obtained represented more than 0.23 billion reads. After assembly, annotation, and operational taxonomic unit clustering, 103, 12, 10, and 12 OTUs were obtained, which belonged to the ITS2, psbA-trnH, matK, and rbcL sequences of the mock lab-made and commercial samples. The analytical results indicated that the sequences of all the prescription ingredients were successfully obtained in the two lab-made samples. The positive control medicinal Panax quinquefolius L. sequence was obtained in HSZY175, while Scutellaria baicalensis Georgi, Lonicera japonica Thunb. Menispermum dauricum DC. and Paeonia lactiflora Pall. were detected in the three commercial samples. The detection results of the other four herbs in different fragments were not all the same. In addition, a total of 28 fungi OTUs, representing 19 families and 20 genera, were obtained from both the commercial and mock lab-made samples. Aspergillus, Cladosporium, and Penicillium dominated among the 20 genera. This study demonstrated that the shotgun metabarcoding method is a powerful tool for the molecular identification of the biological ingredients in Qingguo Wan. It can be used to effectively supplement traditional methods while providing a new technique for the quality evaluation of Qingguo Wan.

Fangchinoline suppresses conjunctival melanoma by directly binding FUBP2 and inhibiting the homologous recombination pathway.

Conjunctival melanoma (CM) is a rare and fatal ocular tumour with poor prognosis. There is an urgent need of effective therapeutic drugs against CM. Here, we reported the discovery of a novel potential therapeutic target for CM. Through phenotypic screening of our in-house library, fangchinoline was discovered to significantly inhibit the growth of CM cells including CM-AS16, CRMM1, CRMM2 and CM2005.1. Further mechanistic experiments indicated that fangchinoline suppressed the homologous recombination (HR)-directed DNA repair by binding with far upstream element binding protein 2 (FUBP2) and downregulating the expression of HR factors BRCA1 and RAD51. In vitro and in vivo antitumour experiments revealed that fangchinoline increased the efficacy of cisplatin by blocking HR factors and reduced the drug dose and toxicity. In conclusion, our work provides a promising therapeutic strategy for the treatment of CM that is worthy of extensive preclinical investigation.

The Diagnosis Performance of the TCM Syndromes of Irritable Bowel Syndrome by Gastroenterologists Based on Modified Simple Criteria Compared to TCM Practitioners: A Prospective, Multicenter Preliminary Study.

PURPOSE: Traditional Chinese medicine (TCM) including Chinese patent medicine has been widely used to treat irritable bowel syndrome (IBS). Syndrome differentiation is the essence of TCM. However, the diagnostic ability of gastroenterologists to detect TCM syndromes in IBS in China remains unknown. The aim of this study was to investigate the ability of gastroenterologists to diagnose the TCM syndromes of IBS based on modified simple criteria compared with TCM practitioners. METHODS: Patients meeting the Rome III criteria for IBS-D or IBS-C were recruited from six tertiary referral centers between January 2016 and December 2017. After learning the diagnosis criteria of the TCM syndromes in IBS, gastroenterologists first diagnosed the syndromes of the enrolled patients. Subsequently, the patients were diagnosed by TCM practitioners. The rate of agreement between the gastroenterologists and TCM practitioners was analyzed. In addition, demographic data and the distribution of TCM syndrome types in IBS were also analyzed. RESULTS: A total of 178 patients (93 males and 85 females), including 131 patients with IBS-D and 47 patients with IBS-C, were enrolled in this study. The rate of agreement of the syndrome diagnosis between the gastroenterologists and TCM practitioners was 84.3%. The diagnosis consistency rates among IBS-D patients and IBS-C patients were 87.0% and 76.5%, respectively. The most common TCM syndrome type in IBS-D patients was liver depression and spleen deficiency syndrome (27.5%), followed by spleen-yang deficiency syndrome (19.8%). Dryness and heat in intestine syndrome was the most common TCM syndrome in IBS-C patients (57.4%). CONCLUSIONS: Gastroenterologists had good diagnostic agreement with TCM practitioners for diagnosing TCM syndrome types in IBS after learning the diagnostic criteria. This knowledge can aid gastroenterologists in selecting suitable Chinese patent medicine to treat IBS.

Traditional Chinese medicine formula Bi-Qi capsule alleviates rheumatoid arthritis-induced inflammation, synovial hyperplasia, and cartilage destruction in rats.

BACKGROUND: Traditional Chinese medicine (TCM) formula Bi-Qi capsule (Bi-Qi) is a commonly prescribed drug to treat rheumatoid arthritis (RA). However, the mechanism of Bi-Qi-mediated amelioration of RA pathogenesis is still a mystery. Collagen induced arthritis (CIA) in rats is an established model that shares many similarities with RA in humans. In this study we investigated the effect of Bi-Qi on the pathogenesis of CIA in rats. METHODS: CIA was developed in Sprague-Dawley (S.D) rats (n = 60, female) and used as a model resembling RA in humans. Rats were treated with a high or moderate dose of Bi-Qi, or methotrexate (MTX). Effects of the treatment on local joint and systemic inflammation, synovial hyperplasia, cartilage destruction, and other main features in the pathogenesis of CIA were analyzed. RESULTS: Inflamed and swollen ankles and joints were observed in arthritic rats, while Bi-Qi or MTX treatment alleviated these symptoms. Only the Bi-Qi moderate dose decreased RA-induced serum levels of tumor necrosis factor-alpha (TNF-α). Both Bi-Qi and MTX reduced the interleukin (IL)-18 serum level. Protein levels of cartilage oligomeric matrix protein and osteopontin in serum, synovium, and cartilage were elevated in arthritic rats, while Bi-Qi alleviated these effects. Synovial hyperplasia, inflammatory cell infiltration in synovium and a high degree of cartilage degradation was observed in RA, and Bi-Qi or MTX alleviated this effect. Bi-Qi at the moderate dose was the most effective in mitigating CIA-related clinical complications. CONCLUSIONS: Our findings showed that Bi-Qi alleviates CIA-induced inflammation, synovial hyperplasia, cartilage destruction, and the other main features in the pathogenesis of CIA. This provides fundamental evidence for the anti-arthritic properties of Bi-Qi and corroborates the use of Bi-Qi TCM formula for the treatment of RA.

Discovery of novel piperonyl derivatives as diapophytoene desaturase inhibitors for the treatment of methicillin-, vancomycin- and linezolid-resistant Staphylococcus aureus infections.

Inhibition of S. aureus diapophytoene desaturase (CrtN) could serve as an alternative approach for addressing the tricky antibiotic resistance by blocking the biosynthesis of carotenoid pigment which shields the bacterium from host oxidant killing. In this study, we designed and synthesized 44 derivatives with piperonyl scaffold targeting CrtN and the structure-activity relationships (SARs) were examined extensively to bring out the discovery of 21b with potent efficacy and better hERG safety profile compared to the first class CrtN inhibitor benzocycloalkane derivative 2. Except the excellent pigment inhibitory activity against wild-type S. aureus, 21b also showed excellent pigment inhibition against four pigmented MRSA strains. In addition, H2O2 killing and human whole blood killing assays proved 21b could sensitize S. aureus to be killed under oxidative stress conditions. Notably, the murine study in vivo validated the efficacy of 21b against pigmented S. aureus Newman, vancomycin-intermediate S. aureus Mu50 and linezolid-resistant S. aureus NRS271.

Semen Ziziphi Spinosae and Fructus Gardeniae extracts synergistically improve learning and memory of a mouse model.

Semen Ziziphi Spinosae (SZS) and Fructus Gardeniae (FG) are two herbs commonly used in traditional Chinese medicine. Previous studies have suggested that Fructus Gardeniae as well as Semen Ziziphi Spinosae are able to regulate the function of the central nervous system. However, their effect on learning and memory has yet to be elucidated. In this study, we examined the effect of SZS and FG on the learning and memory of mice using the methods of step-through and -down passive avoidance tasks and Morris water maze tasks. The results showed that SZS and FG extracts have certain effects on improving the performance of the learning and memory-impaired mouse model. Of note, compound extracts of SZS and FG have a synergistic effect on the learning and memory of mice.

[Effect of compound gardenia oil and jujube seed oil on learning and memory in ovariectomized rats].

OBJECTIVE: To observe the effect of compound of gardenia oil and jujube seed oil learning and memory in ovariectomized rats and its mechanism. METHODS: Animals were randomly divided into six groups: sham group, model group, estrogen group, low dose group, middle dose group and high dose group. The ovariectomized rat models were established by resection of the lateral ovaries. The effect of compound of gardenia oil and jujube seed oil on learning and memory in ovariectomized rats was observed by means of Morris water maze. Acetylcholinesterase (AchE) and nitric oxide synthase (NOS) activities in rat brain were determined. RESULTS: The compound of gardenia oil and jujube seed oil could shorten the incubation period of appearance in castration rats and increase the number passing through Yuan Ping table in ovariectomized rats. As the training time extended, the incubation period of appearance was gradually shortened. The compound of gardenia oil and jujube seed oil could increase NOS activity, and decrease AChE activity in brain of ovariectomized rats. CONCLUSION: The compound of jujube seed oil and gardenia oil could promote the learning and memory in ovariectomized rats. This effect may be related with the increase in activities of NOS, AchE in rat brain.

[Sedative, hypnotic and antiseizure effects of compound gardenia oil and jujube seed oil in mice].

OBJECTIVE: To study the sedative, hypnotic and antiseizure effects of the compound preparation of gardenia oil and jujube seed oil in mice and investigate the interaction of the two drugs in this preparation. METHODS: The compound preparation was administered intragastrically in mice, whose spontaneous activity was observed along with their tolerance of the preparation after long-term administration. The hypnotic effect of the compound was assessed by investigating the changes in the pentobarbital sodium-induced sleeping. The compound was tested for its antiseizure effect in mice with pentetrazole-induced clonic and tonic convulsion. Diazepam was used as the standard control in all experiments. RESULTS: The jujube seed oil, the gardenia oil and their compound all inhibited spontaneous activities of the mice. Compared with diazepam, the compound showed slow action in producing the sedative effect, which increased gradually with prolonged drug administration without obvious drug tolerance responses. The compound and the two oils all showed synergistic action with pentobarbital sodium in inducing sleeping of the mice. Prescription study showed that the compound produced stronger sedative and hypnotic effects than either of the oils. The two oils and the compound did not show significant antiseizure effects in mice. CONCLUSION: The compound of jujube seed oil and gardenia oil has sedative and hypnotic effects in mice, and the two oils in the compound show obvious synergistic effect.