Systems Pharmacology Strategy for the Investigation of Action Mechanisms of Qin Herb Libanotis Buchtormensis (Fisch.) DC. in Bone Diseases.

INTRODUCTION: Qin medicines are medicinal plants growing in habitat around the peak of Qinling Mountain. Their unique curative effects on bone metabolic diseases and pain diseases have been favoured by the local people in clinical trials for thousands of years. Libanotis buchtormensis (Fisch.) DC. (LBD), is one of the popular Qin herbs, which has been widely used for the treatment of various diseases, such as osteoporosis, rheumatic, and cardiovascular diseases. However, due to the multiple compounds in LBD, the underlying molecular mechanisms of LBD remain unclear. OBJECTIVE: This study aimed to systemically investigate the underlying mechanisms of LBD against bone diseases. METHODS: In this study, a systems pharmacology platform included the potential active compound screening, target fishing, and network pharmacological analysis was employed to decipher the action mechanisms of LBD. RESULTS: As a result, 12 potential active compounds and 108 targets were obtained. Furthermore, compound-target network and target-pathway network analysis showed that multi-components interacted with multi-targets and multi-pathways, i.e., MARK signalling pathway, mTORC1 signalling pathway, etc., involved in the regulation of the immune system and circulatory system. These results suggested the mechanisms of the therapeutic effects of LBD on various diseases through most compounds targeted by multiple targets. CONCLUSION: In conclusion, we successfully predicted the LBD bioactive compounds and potential targets, implying that LBD could be applied as a novel therapeutic herb in osteoporosis, rheumatic, and cardiovascular diseases. This work provides insight into the therapeutic mechanisms of LBD for treating various diseases.

Metabolomics analysis of Ligustri Lucidi Fructus at different harvest times during the whole growing period based on ultra-high-performance liquid chromatography with mass spectrometry.

After medicinal market research, it was found that the harvest time of Ligustri Lucidi Fructus (LLF) was chaotic in practice. In order to determine the optimal harvest period of LLF to ensure its pharmacological activity, metabolomics analysis of LLF at different harvest times based on ultra-high-performance liquid chromatography-triple quadrupole-(linear ion trap)-tandem mass spectrometry was established. In this study, 166 differential metabolites (DMs) in 448 metabolites at different harvest times were screened out based on variable importance in projection value, and among them, 94 DMs with regular trends of change in relative content (59 increased and 35 decreased with the growth period) were chosen to further research. The result of the multivariate statistical analysis showed that November was the optimal harvest period of LLF. Additionally, 10-hydroxyligustroside, oleoside 11-methyl ester, and salidroside were screened out to be used as the evaluation indicators of immature LLF, while specnuezhenide, nuezhenoside G13, and neonuezhenide were the evaluation indicators of mature LLF. This study provides fundamental insight for metabolite identification and proposes the best harvest period of LLF to avoid confusion in the medicinal market.

Efficacy and safety of acupuncture for post-COVID-19 depression: a protocol for systematic review and meta-analysis.

INTRODUCTION: Post-COVID-19 depression (PCD) is a possible sequela of COVID-19. Some doctors have used acupuncture to treat PCD, but no systematic review or meta-analysis has yet evaluated its efficacy and safety for the treatment of PCD. The aim of this systematic review is to assess the efficacy and safety of acupuncture therapy for PCD. METHODS AND ANALYSIS: Two reviewers will independently search the Cochrane Central Register of Controlled Trials (CENTRAL), Medline (PubMed), Excerpt Medica Database (EMBASE), China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Chinese Scientific Journal Database (VIP) and Wan-Fang Database from inception to 24 January 2023. Study selection, data extraction and assessment of study quality will be independently performed by two reviewers. If a meta-analysis is appropriate, Review Manager V.5.3 will be used for data synthesis; otherwise, a descriptive analysis will be conducted. Data will be synthesised using a fixed-effects or random-effects model, according to the results of a heterogeneity test. The results will be presented as risk ratios with 95% CIs for dichotomous data, and weighted mean differences or standardised mean differences with 95% CIs for continuous data. ETHICS AND DISSEMINATION: The entire process used for this systematic review does not use private information, so ethical approval is not required. The results of this meta-analysis will be disseminated through publication in a peer-reviewed journal and/or conference presentations. PROSPERO REGISTRATION NUMBER: CRD42022379312.

Changes of root AMF community structure and colonization levels under distribution pattern of geographical substitute for four Stipa species in arid steppe.

The establishment of symbiotic relationship between arbuscular mycorrhizal fungi (AMF) and roots is a mutually beneficial process and plays an important role in plant succession in ecosystems. However, there is less understanding of information about the AMF community in roots under vegetation succession on a large regional scale, especially the spatial variation in the AMF community and its potential ecological functions. Here, we elucidated the spatial variations in root AMF community structure and root colonization along a distribution pattern of four zonal Stipa species in arid and semiarid grassland systems and explored key factors regulating AMF structure and mycorrhizal symbiotic interactions. Four Stipa species established a symbiosis with AMF, and annual mean temperature (MAT) and soil fertility were the main positive and negative driving factors of AM colonization, respectively. The Chao richness and Shannon diversity of AMF community in the root system of Stipa species tended to increase firstly from S. baicalensis to S. grandis and then decreased from S. grandis to S. breviflora. While evenness of root AMF and root colonization showed a trend of increasing from S. baicalensis to S. breviflora, and biodiversity was principally affected by soil total phosphorus (TP), organic phosphorus (Po) and MAT. It is emphasized that Stipa species have certain dependence on AMF, especially in a warming environment, and the root AMF community structure among the four Stipa taxa was different. Additionally, the composition and spatial distribution of root AMF in host plants varied with MAT, annual mean precipitation (MAP), TP and host plant species. These results will broaden our understanding of the relationship between plant and AMF communities and their ecological role, and provide basic information for the application of AMF in the conservation and rehabilitation of forage plants in degraded semiarid grasslands.

Combined Tui na and Western medicine treatment improves pulmonary function and quality of life in patients with amyotrophic lateral sclerosis: A case report.

RATIONALE: Amyotrophic lateral sclerosis is a rare disease that cannot be cured. We report a case of a patient with amyotrophic lateral sclerosis whose pulmonary function and quality of life were improved by a combined tui na treatment and Western medicine. PATIENT CONCERNS: A 48-year-old male was diagnosed with ALS 1 year ago and was treated with western medicine and herbal medicine with no significant effect. This time, he was admitted to our department because of slurred speech, coughing and choking, and weakness of the left upper limb for more than 1 year. INTERVENTION AND OUTCOME: After 1 month of treatment with tui na and traditional western medicine, the patient's lung function and quality of life improved and he was discharged from the hospital. DIAGNOSES: Motor neuron disease. Amyotrophic lateral sclerosis. LESSONS: The physiological function of ALS patients can be improved through the intervention of tui na.

Simultaneous determination and quality evaluation of 16 compounds in Ligustri Lucidi Fructus covering different regions and processed products using ultra-high-performance liquid chromatography-mass spectrometry.

A quantitative analysis method and a chemical pattern recognition method were developed to evaluate raw Ligustri Lucidi Fructus (LLF) from different regions and different processed products. In this study, a comprehensive strategy using ultra-high-performance liquid chromatography-mass spectrometry quantitative analysis method was established for the simultaneous determination of 16 components in 47 batches of LLF covering 19 regions belonging to 8 provinces and 24 batches of different processed products (steamed LLF without auxiliary material, wine-steamed LLF, salt-steamed LLF, and vinegar-steamed LLF). The results of this study indicated that the proposed method was reliable and accurate for the rapid analysis proved by detection limit, quantification limit, precision, and accuracy. Furthermore, principal component analysis and hierarchical cluster analysis were employed to analyze the experimental data, showing that the best-quality samples of 47 batches of raw LLF were S47 (Lantian, Shaanxi), S39 (Pingyang-2, Shandong), S38 (Pingyang-1, Shandong), and S45 (Lingbao, Henan), whereas the worst-quality samples were S7-S16 (Huzhou, Zhejiang). In 24 batches of processed products, the best-quality samples were S48 (salt steamed 2 h), S60 (wine steamed 2 h), and S61 (wine steamed 4 h). Meanwhile, the heat map showed that the contents of triterpenoid saponins, including C16 (ursolic acid), C15 (oleanic acid), and C14 (maslinic acid), were higher than those of other compounds in 71 batches of samples. These results suggested that the quality of raw LLF in the central and northern regions was better than that in the southern regions, and regarding the processed products, different auxiliary materials had little effect on the quality of LLF, but steaming time of 2 h was appropriate. Briefly, this study proposed a multiparameter quantitative analysis method for the overall quality control of raw LLF samples covering different regions in China and different processed LLF.

Discovery and therapeutic implications of bioactive dihydroxylated phenolic acids in patients with severe heart disease and conditions associated with inflammation and hypoxia.

Our initial studies detected elevated levels of 3,4-dihydroxyphenyllactic acid (DHPLA) in urine samples of patients with severe heart disease when compared with healthy subjects. Given the reported anti-inflammatory properties of DHPLA and related dihydroxylated phenolic acids (DPAs), we embarked on an exploratory multi-centre investigation in patients with no urinary tract infections to establish the possible pathophysiological significance and therapeutic implications of these findings. Chinese and Caucasian patients being treated for severe heart disease or those conditions associated with inflammation (WBC ≥ 10 ×109/L or hsCRP ≥ 3.0 mg/L) and/or hypoxia (PaO2 ≤ 75 mmHg) were enrolled; their urine samples were analyzed by HPLC, HPLC-MS, GC-MS and biotransformation assays. DHPLA was detected in urine samples of patients, but undetectable in healthy volunteers. Dynamic monitoring of inpatients undergoing treatment showed their DHPLA levels declined in proportion to their clinical improvement. In DHPLA-positive patients' fecal samples, Proteus vulgaris and P. mirabilis were more abundant than healthy volunteers. In culture, these gut bacteria were capable of reversible interconversion between DOPA and DHPLA. Furthermore, porcine and rodent organs were able to metabolize DOPA to DHPLA and related phenolic acids. The elevated levels of DHPLA in these patients suggest bioactive DPAs are generated de novo as part of a human's defense mechanism against disease. Because DHPLA isolated from Radix Salvia miltiorrhizae has a multitude of pharmacological activities, these data underpin the scientific basis of this medicinal plant's ethnopharmacological applications as well as highlighting the therapeutic potential of endogenous, natural or synthetic DPAs and their derivatives in humans.

Effectiveness and safety of auricular therapy for post-stroke depression: A protocol for systematic review and meta-analysis.

BACKGROUND: Post-stroke depression is a common and serious complication after stroke. Its main clinical manifestations are depression or instability, loss of interest, loss of appetite, sleep disorders, pessimism, and unworthiness, and even suicidal tendencies. Auricular therapy (AT), as part of traditional Chinese acupuncture, has achieved good results in the treatment of depression, but different clinical studies have shown mixed results. Therefore, the aim of this systematic review is to assess the effectiveness and safety of AT for post-stroke depression. METHODS: Two reviewers will electronically search the following databases: the Cochrane Central Register of Controlled Trials; Medline (via PubMed); Excerpt Medica Database; China National Knowledge Infrastructure; Chinese Biomedical Literature Database; Chinese Scientific Journal Database; and Wan-Fang Database from the inception to January 1, 2022. Study selection, data extraction, and assessment of study quality will be performed independently by 2 reviewers. If it is appropriate for a meta-analysis, Review Manager Version 5.3 statistical software will be used; otherwise, a descriptive analysis will be conducted. Data will be synthesized by either the fixed-effects or random-effects model according to a heterogeneity test. The results will be presented as risk ratio with 95% confidence intervals for dichotomous data and weight mean difference or standard mean difference 95% confidence intervals for continuous data. RESULT: This study will provide a comprehensive review of the available evidence for the treatment of AT with post-stroke depression. CONCLUSIONS: The conclusions of our study will provide an evidence to judge whether AT is an effective and safe intervention for patients with post-stroke depression. TRIAL REGISTRATION NUMBER: PROSPERO CRD42021289870.

Poria cocos polysaccharides reduces high-fat diet-induced arteriosclerosis in ApoE-/- mice by inhibiting inflammation.

Atherosclerosis (AS) is a common chronic inflammatory disease of the arteries, which is closely related to dyslipidemia, inflammatory factors, and oxidative stress. Poria cocos polysaccharides (PCP) are one of the main active ingredients of Poria, which has significant pharmacological effects. In this study, the potential protective mechanism of PCP on AS was discussed in the ApoE-/- mice model induced by high-fat diet. These pathological changes were evaluated by H&E and oil red O staining. The levels of pro-inflammatory cytokines in aortic tissue were measured by enzyme-linked immunosorbent assay kit. These protein expressions were detected by Western blot and immunohistochemistry. The results showed that PCP inhibited the serum inflammatory mediators (tumor necrosis factor-α, interleukin-6, and nitric oxide) and lipids (low-density lipoprotein-cholesterol, triglyceride, and total cholesterol) increase. Moreover, PCP also reduced the concentration of malondialdehyde, increased the activity of superoxide dismutase, and improved the pathological changes of the aorta. Finally, PCP inhibited the activation of the TLR4/NF-κB pathway in the aorta and blocked the expression of matrix metalloproteinase 2 and intercellular adhesion molecule 1 proteins. In short, PCP intervenes in AS by reducing inflammatory factors and blood lipid levels.

[Design of moxibustion device for experimental rabbits].

An experimental device is designed to solve the problem of fixing rabbits and providing moxibustion treatment at the same time. The device includes a rabbit fixing box and a moxibustion shelf. The rabbit fixing box and the moxibustion shelf are detachable, and could be used for moxibustion at the chest-back and abdomen of rabbits. A moxibustion device is placed on the moxibustion shelf. The moxibustion device can be moved forward, backward, leftward, rightward, upward and downward on the moxibustion shelf. It meets the requirements of moxibustion at multiple meridians or acupoints on the chest-back and abdomen at the same time. The moxibustion device is equipped with moxa cone or stick, which not only ensures the full burning of moxa, but also prevents the falling of moxa from hurting rabbits. In conclusion, the device has novel and unique structure, is safe and reliable, and easy to operate. It is an innovation in the experimental device of moxibustion, which could promote the animal experiment of moxibustion.

Analysis of the Effect of 60Co-γ Irradiation Sterilization Technology on the Chemical Composition of Saffron Using UPLC and UPLC/Q-TOF-MS.

To evaluate the effect of 60Co-γ irradiation sterilization technology on the chemical composition of saffron, we collected 10 batches of saffron samples and treated them with different irradiation doses. UPLC characteristic chromatogram showed that there was no significant effect of irradiation on 13 common peak areas. The results of cluster analysis and principal component analysis showed that there were no differences in the chemical composition in nonirradiated and irradiated samples. UPLC/Q-TOF-MS identified 40 characteristic components of saffron, and the results showed that all of these were detected in the saffron samples both with and without irradiation. Irradiation doses at or below 10 kGy had no significant effect on the chemical components of saffron. This provides a sound basis for the use of 60Co-γ ray irradiation sterilization technology during the preparation of original powder saffron as a medicinal herb, for the effective destruction of mycotoxin contamination.

Determination of oleanolic and ursolic acid in Chinese herbs using HPLC and γ-CD as mobile phase modifier.

To separate and determine oleanolic acid and ursolic acid, a rapid and accurate HPLC using γ-CD as the mobile phase additive was developed. The effect of CD nature and concentration, and the acidity of the mobile phase on the chromatographic behavior of two bioactive triterpenes were systematically studied. Two bioactive triterpenes were completely separated (R = 3.11) on a Kromasil(®) C(18) column (150×4.6 mm id, 5 µm) with the mobile phase consisting of acetonitrile/0.1% phosphoric acid with 2 mM γ-CD as the mobile phase modifier (60:40, v/v). The flow rate was set at 1.0 mL/min and the eluent was detected at 210 nm for two bioactive triterpenes. The linearity of the method was excellent (r=0.9999) over the studied range of 6-300 µg/mL for oleanolic acid, and 12-600 µg/mL for ursolic acid. The LOD and LOQ were 1.5 and 5.0, 1.0 and 3.0 µg/mL for oleanolic acid and ursolic acid, respectively. The optimized method was successfully applied to separate and determine two bioactive triterpenes in five Chinese herbs. It is concluded that this method could be used for rapid and accurate qualitative and quantitative analysis of the two bioactive triterpenes in Chinese herbs.

[Clinical study on "Jin's three-needling" in treatment of generalized anxiety disorder].

OBJECTIVE: To study the clinical effect of "Jin's three-needling" in the treatment of generalized anxiety disorder. METHODS: Fifty-eight patients with generalized anxiety were randomly assigned to two groups equally, the medication group treated with anti-anxiety drugs and the acupuncture group with "Jin's three-needling". The treatment course was 6 weeks. The clinical effects were evaluated with Hamilton anxiety scale (HAMA), clinical global impression (CGI), and treatment emergent symptom scale (TESS) before treatment and at the end of 2nd, 4th, 6th week of the treatment course. The concentration of 5-hydroxytryptamine (5-HT) in platelet, and plasma levels of corticosterone (CS) and adrenocorticotropic hormone (ACTH) were measured with high performance liquid chromatography-electrochemical detection (HPLC-ED) method before and after treatment. RESULTS: The clinical effects in the two groups were equivalent, while the adverse reaction found in the acupuncture group was less than that in the medication group (P < 0.05). The platelet concentration of 5-HT and plasma ACTH level decreased significantly in both groups after treatment with insignificant difference between the group (P < 0.05). The plasma CS level had no obvious change in the two groups after treatment as compared with that before treatment respectively. CONCLUSION: "Jin's three-needling" shows similar curative effect on generalized anxiety to routine Western medicine but with less adverse reaction, which may be realized through regulating the platelet 5-HT concentration and plasma ACTH level.