Impact of macrophage differentiation on hematopoietic function enhancement by Shenzhu ErKang Syrup.

Shenzhu Erkang Syrup (SZEK) is a traditional Chinese medicine that improves spleen and stomach function, tonifying the Qi and activating the blood; however, its therapeutic effects in hematopoietic dysfunction and their underlying mechanism remain unexplored. In this study, mice were given cyclophosphamide (100 mg/kg) by intraperitoneal injections for three days to produce hematopoietic dysfunction model. We investigated the hematopoietic effect and mechanism of SZEK in mice with hematopoietic dysfunction via histopathological examination, flow cytometry, enzyme-linked immunosorbent assay, and Western blotting combined with intestinal flora and serum metabolomics analysis. In mice with hematopoietic dysfunction, SZEK (gavage, 0.3 mL/25 g) alleviated pathological damage to the bone marrow and spleen; increased the number of naïve cells (Lin-), hematopoietic stem cells (Lin-Sca-1+c-Kit+), long-term self-renewing hematopoietic stem cells (Lin-Sca-1+c-Kit+CD48-CD150+), B lymphocytes (CD45+CD19+), and macrophages (CD11b+F4/80+) in the bone marrow; and reduced inflammation. Preliminary intestinal flora and serum metabolome analyses indicated that the pro-hematopoietic mechanism of SZEK was associated with macrophage differentiation. Further validation revealed that SZEK promoted hematopoiesis by decreasing the number of M2 macrophages and inhibiting the secretion of negative hematopoietic regulatory factors in mice with hematopoietic dysfunction.

Protective Effects of Danmu Extract Syrup on Acute Lung Injury Induced by Lipopolysaccharide in Mice through Endothelial Barrier Repair.

OBJECTIVE: To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism. METHODS: Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 ß in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis. RESULTS: DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 ß (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01). CONCLUSIONS: DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.

Successful treatment of severe MSUD in Bckdhb-/- mice with neonatal AAV gene therapy.

Maple syrup urine disease (MSUD) is rare autosomal recessive metabolic disorder caused by the dysfunction of the mitochondrial branched-chain 2-ketoacid dehydrogenase (BCKD) enzyme complex leading to massive accumulation of branched-chain amino acids and 2-keto acids. MSUD management, based on a life-long strict protein restriction with nontoxic amino acids oral supplementation represents an unmet need as it is associated with a poor quality of life, and does not fully protect from acute life-threatening decompensations or long-term neuropsychiatric complications. Orthotopic liver transplantation is a beneficial therapeutic option, which shows that restoration of only a fraction of whole-body BCKD enzyme activity is therapeutic. MSUD is thus an ideal target for gene therapy. We and others have tested AAV gene therapy in mice for two of the three genes involved in MSUD, BCKDHA and DBT. In this study, we developed a similar approach for the third MSUD gene, BCKDHB. We performed the first characterization of a Bckdhb-/- mouse model, which recapitulates the severe human phenotype of MSUD with early-neonatal symptoms leading to death during the first week of life with massive accumulation of MSUD biomarkers. Based on our previous experience in Bckdha-/- mice, we designed a transgene carrying the human BCKDHB gene under the control of a ubiquitous EF1α promoter, encapsidated in an AAV8 capsid. Injection in neonatal Bckdhb-/- mice at 1014 vg/kg achieved long-term rescue of the severe MSUD phenotype of Bckdhb-/- mice. These data further validate the efficacy of gene therapy for MSUD opening perspectives towards clinical translation.

Study of the Analgesic Potential of the Ethanolic Extract of Moroccan Cistus ladanifer L.

AIMS: The study aimed to analyze the analgesic activity of Cistus ladanifer L. BACKGROUND: Cistus ladanifer L. is a fragrant shrub of the Cistaceae family widespread in the Mediterranean basin, it has various biological activities, including antidiabetic and antihypertensive effects. OBJECTIVES: The objective of this work was to study the phytochemical profile, the acute toxicity and the analgesic power of the ethanolic extract of the species Cistus ladanifer L. (C. ladanifer) collected in Northern Morocco. METHODS: The evaluation of antinociceptive activity in mice was performed using two validated models, the formalin-induced paw-licking model and the acetic acid-provoked writhing test. RESULTS: According to the results, five phenolic compounds were identified in the ethanolic extract by HPLC-MS/MS. As regards the acute toxicity study, the results showed no mortality or clinical symptoms in mice treated to compare the control group at doses up to 5,000 mg/kg BW. Regarding the analgesic effect, the ethanolic extract at the doses of 400 and 800 mg/kg, BW showed a statistically significant (p <0.05) and dose-dependent analgesic effect in two nociceptive tests. On the other hand, in the syrup of ethanolic extract at the dose of 800 mg/kg, BW expressed the most superior pain-inhibiting effect in both tests, producing an analgesic effect equivalent to that of the reference drug (indomethacin). CONCLUSION: These findings provide pharmacological justification that might aid in the development of a natural anti-nociceptive medication as an alternative to chemical analgesic drugs.

[Efficacy and safety of Regan Syrup in treatment of common cold (wind-heat syndrome):a multicenter, randomized, double-blind, double-dummy, placebo and positive drug-controlled, parallel, phase â ¡b clinical trial].

Regan Syrup has the effect of clearing heat, releasing exterior, benefiting pharynx and relieving cough, and previous phase Ⅱ clinical trial showed that the efficacy of Regan Syrup high-dose and low-dose groups was better than that of the placebo group, and there was no statistically significant difference in the safety between the three groups. The present study was conducted to further investigate the efficacy and safety of the recommended dose(20 mL) of Regan Syrup in the treatment of common cold(wind-heat syndrome). Patients who met the inclusion and exclusion criteria were selected and divided into the test group(Regan Syrup+Shufeng Jiedu Capsules placebo), positive drug group(Regan Syrup placebo+Shufeng Jiedu Capsules) and placebo group(Regan Syrup placebo+Shufeng Jiedu Capsules placebo) at a 1∶1∶1 using a block randomization method. The course of treatment was 3 days. A total of 119 subjects were included from six study centers, 39 in the test group, 40 in the positive drug group and 40 in the placebo group. The onset time of antipyretic effect was shorter in the test group than in the placebo group(P≤0.01) and the positive drug group, but the difference between the test group and the positive drug group was not significant. The test group was superior to the positive drug group in terms of fever resolution(P<0.05), and had a shorter onset time of fever resolution than the placebo group, but without obvious difference between the two groups. Compared to the positive drug group, the test group had shortened disappearance time of all symptoms(P≤0.000 1). In addition, the test group was better than the positive drug group and the placebo group in relieving symptoms of sore throat and fever(P<0.05), and in terms of clinical efficacy, the recovery rate of common cold(wind-heat syndrome) was improved in the test group compared to that in the placebo group(P<0.05). On the fourth day after treatment, the total TCM syndrome score in both test group and positive drug group was lower than that in the placebo group(P<0.05). There was no significant difference in the incidence of adverse events between three groups and none of them experienced any serious adverse events related to the study drug. The results indicated that Regan Syrup could shorten the onset time of antipyretic effect, reduce the time of fever resolution, alleviate the symptoms such as sore throat and fever caused by wind-heat cold, reduce the total score of Chinese medicine symptoms, and improve the clinical recovery rate with good safety.

Fecal microbiota transplantation confirmed that 919 Syrup reduced the ratio of erucamide to 5-AVAB in hippocampus to alleviate postpartum depression by regulating gut microbes.

Background: Postpartum depression has a crucial impact on the physical and psychological comfort and the work of postnatal women, the growth and development of infants and mental health in adulthood. Finding a safe and effective anti-postnatal depression drug is currently an important research goal in this field. Methods: In this study, the forced swimming test (FST) and tail suspension test (TST) were used to evaluated the depressive behaviors of mice, and the changes of metabolites and intestinal microflora in mice with postpartum depression were examined through non-target metabolomics and 16S RNA sequencing respectively. Results: We found that traditional Chinese medicine compound 919 Syrup could alleviate postpartum depression in mice and inhibit the elevated erucamide level in depressive hippocampus. However, mice treated with antibiotics were not sensitive to the anti-postnatal depression effect of 919 Syrup, and the level of 5-aminovaleric acid betaine (5-AVAB) in their hippocampus was significantly decreased. Transplanting fecal microflora treated with 919 Syrup could effectively improve the depressive behaviors of mice, upregulate the level of gut-derived 5-AVAB in the hippocampus, and downregulate the level of erucamide. Erucamide was significantly negatively correlated with increased Bacteroides in intestine after 919 Syrup treatment or fecal transplantation, and significantly positively correlated with Ruminococcaceae UCG-014 which was increased in feces of mice with postpartum depression. The increase of Bacteroides, Lactobacillus, and Ruminiclostridium in intestine after fecal transplantation had a clearly positive correlation with 5-AVAB. Conclusion: In brief, 919 Syrup may downregulate the ratio of hippocampal metabolites erucamide to 5-AVAB by regulating intestinal flora to alleviate postpartum depression, laying a scientific foundation for future pathological research and development of therapeutic drugs for postpartum depression.

FTIR-ATR detection method for emerging C3-plants-derivated adulterants in honey: Beet, dates, and carob syrups.

The European Union Publications Office has recently presented a report on the European Union's coordinated action with the Joint Research Centre to determine certain fraudulent practices in the honey sector, in which it has been indicated that 74% of the samples analyzed, imported from China, and 93% of the samples analyzed, imported from Turkey, the two largest honey producers worldwide, presented at least one indicator of exogenous sugar or suspicion of being adulterated. This situation has revealed the critical state of the problem of honey adulteration worldwide and the need to develop analytical techniques for its detection. Even though the adulteration of honey is carried out in a general way with sweetened syrups derived from C4 plants, recent studies have indicated the emerging use of syrups derived from C3 plants for the adulteration of honey. This kind of adulteration makes it impossible to analyze its detection using official analysis techniques. In this work, we have developed a fast, simple, and economical method based on the Fourier transform infrared spectroscopy technique, with attenuated total reflectance, for the qualitative, quantitative, and simultaneous determination of beetroot, date, and carob syrups, derived from of C3 plants; whose available bibliography is very scarce and analytically not very conclusive for its use by the authorities. The proposed method has been based on the establishment of the spectral differences between honey and the mentioned syrups at eight different points in the spectral region between 1200 and 900 cm-1 of the mid-infrared, characteristic of the vibrational modes of carbohydrates in honey, which allows the pre-discrimination of the presence or absence of the syrups studied, and their subsequent quantification, with precision levels lower than 2.0% of the relative standard deviation and relative errors lower than 2.0% (m/m).

Melatonin improves behavioral parameters and oxidative stress in zebrafish submitted to a leucine-induced MSUD protocol.

Maple syrup urine disease (MSUD) is an inherited metabolic disorder caused by a deficiency in branched-chain alpha-ketoacid dehydrogenase complex (BCKAC). The treatment is a standard therapy based on a protein-restricted diet with low branched-chain amino acids (BCAA) content to reduce plasma levels and, consequently, the effects of accumulating their metabolites, mainly in the central nervous system. Although the benefits of dietary therapy for MSUD are undeniable, natural protein restriction may increase the risk of nutritional deficiencies, resulting in a low total antioxidant status that can predispose and contribute to oxidative stress. As MSUD is related to redox and energy imbalance, melatonin can be an important adjuvant treatment. Melatonin directly scavenges the hydroxy radical, peroxyl radical, nitrite anion, and singlet oxygen and indirectly induces antioxidant enzyme production. Therefore, this study assesses the role of melatonin treatment on oxidative stress in brain tissue and behavior parameters of zebrafish (Danio rerio) exposed to two concentrations of leucine-induced MSUD: leucine 2 mM and 5mM; and treated with 100 nM of melatonin. Oxidative stress was assessed through oxidative damage (TBARS, DCF, and sulfhydryl content) and antioxidant enzyme activity (SOD and CAT). Melatonin treatment improved redox imbalance with reduced TBARS levels, increased SOD activity, and normalized CAT activity to baseline. Behavior was analyzed with novel object recognition test. Animals exposed to leucine improved object recognition due to melatonin treatment. With the above, we can suggest that melatonin supplementation can protect neurologic oxidative stress, protecting leucine-induced behavior alterations such as memory impairment.

Evaluation of the effectiveness of Lactuca Sativa syrup in controlling pain after periodontal flap surgery: a split-mouth, randomized, double-blind placebo-controlled trial.

OBJECTIVES: Effective pain control after oral surgeries including periodontal flap surgery is one of the biggest problems in the periodontology field. The use of Nonsteroidal Anti-inflammatory Drugs (NSAIDs) to reduce pain after periodontal flap surgery is common, but these have some adverse side effects such as impaired platelet function and causing digestive problems. Today, the tendency to use omedicinal plants is more than synthetic drugs due to their safety. Therefore, we designed a split-mouth randomized controlled clinical trial to evaluate the effects of Lactuca Sativa (L. Sativa) syrup as an adjunct therapy in reducing pain after periodontal flap surgery. METHODS: This split-mouth, randomized, double-blind, placebo-controlled trial was performed on 26 subjects. Patients were assigned for two surgery. Primary surgery was performed on the right maxilla and after 30 days, secondary surgery was performed on the left maxilla. In primary surgery, patients consumed L. Sativa syrup (3 times a day for 72 h) and in secondary surgery, patients consumed placebo syrup (3 times a day for 72 h). Pain intensity was measured at 6, 12, 24, 48, and 72 h after a periodontal flap surgery in both surgeries using the Visual Analogue Scale (VAS). All patients received their routine drugs, including analgesics. The number of analgesics used after surgery was recorded. Statistical analysis of t-test was used to compare the results of the two surgery. RESULTS: The results showed that the mean pain based on VAS score at 6, 12, 24, 48 and 72 h after primary periodontal flap surgery was significantly reduced compared to the secondary periodontal flap surgery (p<0.001). The results also showed that the use of analgesics after 72 h of surgery was significantly reduced in the primary periodontal flap surgery compared to the secondary periodontal flap surgery (p<0.001). CONCLUSIONS: According to the results of this study, L.Sativa syrup can be effective as adjuvant therapy in reducing pain after periodontal flap surgery.

Efficacy and safety of add-on Viola odorata L. in the treatment of COVID-19: A randomized double-blind controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Severe Acute Respiratory Syndrome (SARS) due to the novel coronavirus has become the highest priority that threatens human health. This situation demands widespread vaccination and the innovation of new therapeutic methods. Despite drug discoveries, the need for approving new medicaments is felt because of adverse effects and lack of efficacy. Several medicinal plants including Viola odorata L. are recommended in traditional Persian medicine for alleviating respiratory infection symptoms. Recent studies showed anti-inflammatory, antioxidant, anti-asthmatic, antitussive, analgesic, and antibacterial activities of sweet violet. These enhance respiratory functions, reduce pulmonary inflammation, and decline mucous membrane edema. This study aimed to evaluate the efficacy of sweet violet syrup in alleviating the manifestations of COVID-19 infection. MATERIAL AND METHODS: A randomized parallel-group double-blind controlled trial was conducted at Al-Zahra general hospital, Isfahan, Iran. A total of 108 outpatients were enrolled in the study. The patients were randomly allocated to intervention and placebo groups, with 54 patients in each group. The allocation was concealed using sealed opaque envelopes. The intervention group received violet syrup and the control group received placebo syrup, an add-on to the conventional treatment. The outcomes were COVID-19 manifestations, such as dyspnea, cough, myalgia, headache, and diarrhea, considered as outcomes of the study and were evaluated twice using a visual analog scale before the intervention and after 7 days, at the end of the study. Patients were followed daily by phone calls to monitor proper drug consumption and possible side effects. RESULTS: No significant difference was between groups regarding demographic characteristics and vital signs before and after the treatment. Although all symptoms have improved significantly in both groups, patients who received violet syrup recovered faster and the mean severity scores of cough (P = 0.025), myalgia (P = 0.036), headache (P = 0.037), and diarrhea (P = 0.044) decreased greater in comparison to control group. CONCLUSION: This study, the first clinical trial on the effectiveness of Viola odorata on SARS-CoV-2 patients, showed that Viola odorata L. effectively controls prevalent manifestations of COVID-19 including cough, myalgia, headache, and diarrhea. Regarding this survey, the violet syrup can be mentioned as a complementary treatment for viral influenza-like infections in which cough, myalgia, headache, and diarrhea are prominent.

UPLC-Q-TOF-MS and UPLC-QQQ-MS were used for the qualitative and quantitative analysis of oligosaccharides in Fufang Ejiao Syrup.

Fufang Ejiao Syrup (FES) is a syrup made from Colla Corii Asini (CCA) and four botanicals (Codonopsis Radix (CR), Ginseng Radix et Rhizoma Rubra (GRRR), Rehmanniae Radix Praeparata (RRP) and Crataegi Fructus (CF)) as a result of modern processing and refining technology. FES has a lengthy history and is frequently used in clinical practice. Modern pharmacological studies have confirmed that oligosaccharides in any of the main medicinal herbs of FES, such as CR, GRRR, and RRP, have significant immune-enhancing effects. Therefore, the oligosaccharide component in FES could be its important pharmacologic substance, however, no studies on the content, structural analysis and source attribution of oligosaccharides in FES have been reported. The objective of this study is to systematically analyze the oligosaccharide in FES, compare the differences of the major oligosaccharides in different batches of FES produced by one manufacturer, and construct the content determination method for determining the content of the major oligosaccharides in FES, to provide technical support for FES quality assessment. This analysis revealed that a total of 13 oligosaccharides were identified from the FES, including 3 disaccharides, 4 trisaccharides, 3 tetrasaccharides, and 3 pentasaccharides. The constructed UPLC-QQQ-MS fingerprint of FES oligosaccharide is simple, stable, and reproducible, making it a useful tool for assessing FES's quality. There was a significant difference between the oligosaccharide fingerprints of 16 batches of FES,the results of fingerprint analysis combined with the statistical analysis suggested that the differences in stachyose, sucrose and raffinose contents in FES may be the reason for the great variations in oligosaccharide fingerprints of different batches of FES. For the 5 oligosaccharides in FES, the UPLC-QQQ-MS technique showed significant linearity in the linear range, along with good stability, repeatability, and recovery. Mannotriose was found to be higher in FES, followed by sucrose and stachyose, while kestose and raffinose were relatively lower. The results of this study reveal that oligosaccharides are important components of FES, and the method of fingerprinting and content determination constructed has strong practical value and is expected to be used for FES quality control.

[Optimization and evaluation of Xiaoer Pudilan Xiaoyan Syrup based on characterization of material properties].

According to the taste analysis of Pudilan Xiaoyan Oral Liquid, the unpleasant taste of the oral liquid is mainly caused by the inherent taste of Chinese medicine and the taste introduced in the preparation process, which leads to its unpopularity among children. Therefore, aiming at the special children patient group, Xiaoer Pudilan Xiaoyan Syrup was developed via technology optimization and dosage form improvement to improve the unpleasant taste and enhance the medication compliance among children. Based on the material properties of Pudilan Xiaoyan Oral Liquid and Xiaoer Pudilan Xiaoyan Syrup extracts, the authors compared the properties(pH, density, turbidity, viscosity, chromaticity, particle size), taste, content of five quality markers and in vivo pharmacokinetic characteristics of these two preparations, to evaluate the suitability of Xiaoer Pudilan Xiaoyan Syrup. The results showed that compared with those of Pudilan Xiaoyan Oral Liquid, the pH, density, turbidity, viscosity and chromaticity of Xiaoer Pudilan Xiaoyan Syrup were significantly changed, and the unpleasant taste was reduced by 26%; the transfer rate of the main active ingredients chicoric acid was increased, while the transfer rate of baicalin had small difference from that of the oral liquid. In addition, pharmacokinetics revealed that the total absorption amount of baicalin in vivo was higher, and the time to peak T_(max) of baicalin and oroxindin in the syrup and the mean residence time MRT_(last )of corynoline in vivo were significantly prolonged. The absorption degree of Xiaoer Pudilan Xiaoyan Syrup and Pudilan Xiaoyan Oral Liquid in the body was the same: baicalin>oroxindin>corynoline. The new dosage form process was simpler than that of the original dosage form, safe, environmentally friendly, reasonable and feasible, meeting the mass production demand. This provided a basis for the reasonable and scientific optimization of Xiaoer Pudilan Xiaoyan Syrup, and also laid a foundation for its further safe and rational use, so as to expand the clinical application in children.

Determination of six core components from Mahuang Xuanfei Zhike syrup in rat plasma and tissues by UPLC-MS/MS: Application to a pharmacokinetics and tissue distribution study.

Mahuang Xuanfei Zhike (MXZ) syrup, a Chinese patent medicine, has been widely used in the clinical treatment of cough. However, there is no reported method for the quantitative analysis of the effective components of MXZ syrup in biological samples. In this study, the effective components of MXZ syrup were screened by network pharmacology and molecular docking technology. A sensitive and rapid ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established to test the active components of MXZ syrup in rat plasma and tissue homogenates, including ephedrine, amygdalin, chlorogenic acid, harpagoside, forsythin and forsythoside A. Chromatographic separation was performed on a Waters Acquity UPLC HSS T3 column (2.1 × 50 mm, 1.8 µm) and the mass analysis was conducted using a Waters Xevo TQ mass spectrometer using multiple reaction positive and negative ion simultaneous monitoring mode. The results showed that the linearity ranged from 0.3 to 409.4 ng/ml. The extraction recoveries were all <8.33%, and the matrix effects were all <8.45, which met the requirements. The pharmacokinetic and tissue distribution results indicated that the main active components of MXZ syrup were absorbed quickly and eliminated slowly in vivo, and there may be a reabsorption process.

CGX, a standardized herbal syrup, inhibits colon-liver metastasis by regulating the hepatic microenvironments in a splenic injection mouse model.

Background: Colon-liver metastasis is observed in approximately 50% of patients with colorectal cancer and is a critical risk factor for a low survival rate. Several clinical studies have reported that colon-liver metastasis is accelerated by pathological hepatic microenvironments such as hepatic steatosis or fibrosis. Chunggan syrup (CGX), a standardized 13-herbal mixture, has been prescribed to patients with chronic liver diseases, including fatty liver, inflammation and fibrotic change, based on preclinical and clinical evidence. Aim of the study: In the present study, we investigated anti-liver metastatic the effects of CGX in a murine colon carcinoma (MC38)-splenic injection mouse model. Materials and methods: C57BL/6N mice were administered with CGX (100, 200 or 400 mg/kg) for 14 days before or after MC38-splenic injection under normal and high-fat diet (HFD) fed conditions. Also, above experiment was repeated without MC38-splenic injection to explore underlying mechanism. Results: The number of tumor nodules and liver weight with tumors were sup-pressed by preadministration of CGX in both normal and HFD fed mice. Regarding its mechanisms, we found that CGX administration significantly activated epithelial-cadherin (E-cadherin), but decreased vascular endothelial-cadherin (VE-cadherin) in hepatic tissues under MC38-free conditions. In addition, CGX administration significantly reduced hepatic steatosis, via modulation of lipolytic and lipogenic molecules, including activated adenosine monophosphate activated protein kinase (AMPK) and peroxisome proliferator activated receptor-alpha (PPARα). Conclusion: The present data indicate that CGX exerts an anti-colon-liver metastatic property via modulation of hepatic lipid related microenvironments.

Consumption of Micronutrient Powder, Syrup or Fortified Food Significantly Improves Zinc and Iron Status in Young Mexican Children: A Cluster Randomized Trial.

The objective of this study was to compare the effect of three micronutrient products on biomarkers of iron and zinc status of Mexican children 6−12 months of age. As part of research to improve the impact of a national program, 54 communities were randomly assigned to receive: (1) fortified food (FF), provided by the program at the time, or (2) micronutrient powders (MNP) or (3) syrup. Each product contained 10 mg each of zinc and iron, plus other micronutrients. Children consumed the product 6 days/week for four months. Primary outcomes were changes in serum zinc, ferritin, soluble transferrin receptor, hemoglobin concentrations, and their deficiencies. Zinc concentration increased significantly from baseline to follow-up in all groups, with the largest change in the syrup group (geometric mean difference: +4.4 µmol/L; 95%CI: 3.2, 5.5), followed by MNP (+2.9 µmol/L; 95%CI: 2.1, 3.6) and FF (+0.9 µmol/L; 95%CI: 0.3, 1.6). There was a significant increase in hemoglobin concentration (+5.5 g/L; 2.5, 8.4) and a significant reduction in anemia prevalence (44.2% to 26.8%, p < 0.01) only in the MNP group. Compliance differed significantly among groups (MNP vs. FF, p = 0.04; MNP vs. syrup, p = 0.04), but may not fully explain the greater improvement in zinc and iron status in the syrup and MNP groups. The food matrix may influence nutrient utilization from supplements.

Mechanism of Shiliu Buxue Syrup for anemia using integrated metabolomics and network pharmacology.

For many years, Shiliu Buxue Syrup (SLBXS) has been used in the treatment of anemia in Xinjiang, China. However, the potential therapeutic mechanism of SLBXS in the treatment of anemia remains unclear. We qualitatively analyzed the ingredients of SLBXS and predicted the underlying mechanisms by network pharmacology. A mice model of anemia was established by subcutaneous injection of 1-Acetyl-2-phenylhydrazine (APH). Spleen metabolomics was performed to screen potential biomarkers and pathways related to anemia. Furthermore, core targets of crucial pathways were experimentally validated. Finally, molecular docking was used for predicting interactions between compositions and targets. Network pharmacology indicated that the 230 SLBXS ingredients may affect 141 target proteins to regulate the PI3K/AKT and HIF-1 signaling pathways. Metabolomics revealed that SLBXS could mediate 30 biomarkers, such as phosphoric acid, l-pyroglutamic acid, alpha-Tocopherol, 1-stearoyl-rac-glycerol, and dihydroxyacetone phosphate, to regulate drug metabolism-other enzymes, glutathione metabolism, glycolysis or gluconeogenesis, nicotinate and nicotinamide metabolism, nitrogen metabolism, and purine metabolism. Western blot indicated that SLBXS can regulate the protein expression levels of AKT1, Bcl2, Caspase3, HIF-1α, VEGF-A, and NOS2. The molecular docking revealed that most of the compositions had a good binding ability to the core targets. Based on these findings, we speculate that SLBXS treats anemia mainly by modulating the PI3K/AKT and HIF-1 pathways and glutathione and glycolytic metabolisms.

[Optimization of extraction process of Children's Qingfei Zhisou Syrup based on pharmacodynamics].

This study determined the extraction rates of indirubin in Indigo Naturalis by ethanol reflux extraction method and water extraction method. The pharmacodynamic study against cough induced by ammonia water in the mouse model and the cough induced by citric acid in the guinea pig model were performed to optimize the extraction process of the sovereign medicinal Indigo Naturalis and the whole prescription of Children's Qingfei Zhisou Syrup. The extraction rate of indirubin by the ethanol reflux method was 51.89%, and indirubin was not detected in the product of water extraction. Two samples of Children's Qingfei Zhisou Syrup prepared with different methods can prolong the incubation period of cough and suppress the frequency of coughs in pharmacodynamic experiments. In terms of prolonging the incubation period of cough, the two samples prepared with different methods had no significant difference. In terms of reducing the frequency of coughs, the high-dose Five kinds of ethanol extracts such as indigo naturalis and three kinds of water extracts such as gypsum had better effect against the citric acid-induced cough of guinea pigs than other samples(P<0.05). The extraction rate of indirubin in Children's Qingfei Zhisou Syrup sample prepared with ethanol was higher than that with water. The two samples of Children's Qingfei Zhisou Syrup prepared with the two methods showed good antitussive effects. The sample prepared with 5 ingredients(including Indigo Naturalis) extracted with ethanol and 3 ingredients(including Gypsum Fibrosum) extracted with water had better alleviation effect on the citric acid-induced cough of guinea pig than the whole water extract sample. In conclusion, the optimum extraction scheme is ethanol extraction for 5 ingredients including Indigo Naturalis in combination with water extraction for 3 ingredients including Gypsum Fibrosum, and the Children's Qingfei Zhisou Syrup produced in this manner has better antitussive efficacy.

[Establishment and verification of quality evaluation method of Jizhi Syrup based on quantitative analysis of multi-components by single marker].

A quantitative analysis of multi-components by single marker(QAMS) method was established for the simultaneous determination of ephedrine hydrochloride, protocatechuic acid, 5-caffeoylquinic acid, 4-hydroxybenzoic acid, naringin, neohesperidin, glycyrrhizic acid, and praeruptorin A in Jizhi Syrup by high performance liquid chromatography(HPLC) with ultraviolet multi-wavelength detection system, and its feasibility in quality evaluation of Jizhi syrup was verified. With naringin as the internal reference substance, the relative correction factors and chromatographic peak localization methods of other seven components were respectively established at 210, 254, 280, and 320 nm. The method reproducibility was validated, and the result of QAMS were compared with those obtained by the external standard method(ESM) to verify the accuracy and feasibility of the method. The relative correction factors of ephedrine hydrochloride, protocatechuic acid, 5-caffeoylquinic acid, 4-hydroxybenzoic acid, neohesperidin, glycyrrhizic acid, and praeruptorin A with naringin as reference were 0.846, 0.582, 0.608, 0.293, 0.913, 2.207, and 0.940, respectively, which presented excellent reproducibility under different experimental conditions. Furthermore, QAMS and ESM showed no significant difference in the results for 15 batches of samples. Except protocatechuic acid and 5-caffeoylquinic acid, other six compounds were the exclusive components of single medicinal materials. In addition, glycyrrhizic acid and praeruptorin A were identified in the Jizhi Syrup for the first time, filling up the blank of no component detected in Glycyrrhizae Radix et Rhizoma and Peucedani Radix. The method established in this study is convenient, efficient, specific, accurate, and reliable, which can comprehensively and effectively evaluate the quality of Jizhi Syrup to ensure the safety and efficacy of this drug in clinical application.

Corrigendum: Efficacy and Safety of Shenqu Xiaoshi Oral Liquid Compared With Domperidone Syrup in Children With Functional Dyspepsia.

[This corrects the article DOI: 10.3389/fphar.2022.831912.].

Brightening effect of Ziziphus jujuba (jujube) fruit extract on facial skin: A randomized, double-blind, clinical study.

Ziziphus jujuba Mill. (jujube) is an invaluable medicinal plant in traditional and modern medicine. Jujube syrup is a complex of herbal extracts including Z. jujuba, Berberis vulgaris, Rhus coriaria, Prunus domestica, and Rosa damascene. The purpose of the present study was to formulate and investigate the efficacy and safety of jujube syrup on brightening of facial skin. In this randomized, double-blind, controlled clinical study, 46 participants consumed jujube syrup or placebo (23 in each group) twice a day for 8 weeks. The number of pigments, area of pigmentation, and physician's global assessment score (PGAS) were evaluated at baseline and after 8 weeks. The results showed the amounts of total phenolics and flavonoids were 81.97 ± 0.25 and 4.98 ± 1.04 mg/ml, respectively. The amounts of organic acids (gallic acid and chlorogenic acid) were quantified at 1140 ± 17.65 and 1520 ± 25.77 µg/ml, respectively. The amounts of total phenolic and flavonoids were stable under accelerated conditions. Eight weeks after treatment, the number of pigment counts reduced to 0.545 ± 0.307 compared to the placebo group. Moreover, the pigmented area and its percentages were significantly reduced to 0.556 ± 0.285 and 0.561 ± 0.288 in jujube syrup compared with placebo, respectively. Jujube syrup is efficient and safe for treating hyperpigmentation of the face.