Gut microbiota-based discovery of Houttuyniae Herba as a novel prebiotic of Bacteroides thetaiotaomicron with anti-colitis activity.

Ulcerative colitis (UC) represents an inflammatory disease characterized by fluctuations in severity, posing substantial challenges in treatment. The gut microbiota plays a pivotal role in the pathogenesis of UC. This study sought to identify drugs specifically targeting the gut microbiota to mitigate UC. We initiated a meta-analysis on gut microbiota in UC patients to identify UC-associated bacterial strains. Subsequently, we screened 164 dietary herbal medicines in vitro to identify potential prebiotics for the UC-associated bacterium, Bacteroides thetaiotaomicron. The DSS-induced colitis mouse model was utilized to evaluate the anti-colitis efficacy of the identified dietary herbal medicine. Full-length 16 S rRNA amplicon sequencing was employed to observe changes in gut microbiota following dietary herbal medicine intervention. The relative abundance of Bacteroides was notably diminished in UC patients compared to their healthy counterparts. B. thetaiotaomicron exhibited an inverse relationship with UC symptoms, indicating its potential as an anti-colitis agent. In vitro assessments revealed that H. Herba significantly bolstered the proliferation of B. thetaiotaomicron. Further experiments showed that treating DSS-induced mice with an aqueous extract of H. Herba considerably alleviated colitis indicators such as weight loss, colon shortening, disease activity score (DAI), and systemic inflammation. Microbial analysis revealed B. thetaiotaomicron as the sole bacterium substantially augmented by H. Herba in vivo. Overall H. Herba emerges as a promising prebiotic for B. thetaiotaomicron, offering significant anti-colitis benefits. Employing a gut microbiota-centric approach proves valuable in the quest for drug discovery.This study provides a new paradigm for drug discovery that targets the gut microbiota to treat UC.

Exploration of the Dynamic Variations of the Characteristic Constituents and the Degradation Products of Catalpol during the Process of Radix Rehmanniae.

Radix Rehmanniae (RR), a famous traditional Chinese medicine (TCM) widely employed in nourishing Yin and invigorating the kidney, has three common processing forms in clinical practice, including fresh Radix Rehmanniae (FRR), raw Radix Rehmanniae (RRR), and processed Radix Rehmanniae (PRR). However, until now, there has been less exploration of the dynamic variations in the characteristic constituents and degradation products of catalpol as a representative iridoid glycoside with the highest content in RR during the process from FRR to PRR. In this study, an ultra-performance liquid chromatography coupled with photodiode array detector (UPLC-PDA) method was successfully established for the simultaneous determination of ten characteristic components to explore their dynamic variations in different processed products of RR. Among them, iridoid glycosides, especially catalpol, exhibited a sharp decrease from RRR to PRR. Then, three degradation products of catalpol were detected under simulated processing conditions (100 °C, pH 4.8 acetate buffer solution), which were isolated and identified as jiofuraldehyde, cataldehyde, and norviburtinal, respectively. Cataldehyde was first reported as a new compound. Moreover, the specificity of norviburtinal in self-made PRR samples was discovered and validated, which was further confirmed by testing in commercially available PRR samples. In conclusion, our study revealed the decrease in iridoid glycosides and the production of new degradation substances during the process from FRR to PRR, which is critical for unveiling the processing mechanism of RR.

Efficacy and safety of acupuncture in post-stroke constipation: a systematic review and meta-analysis.

Background and objective: Post-stroke constipation (PSC) is a common complication of strokes that seriously affects the recovery and quality of life of patients, and effective treatments are needed. Acupuncture is a viable treatment option, but current evidence is insufficient to support its efficacy and safety. This study aims to evaluate the efficacy and safety of acupuncture in the treatment of PSC. Methods: A systematic search of eight databases was conducted to identify PSC-related randomized clinical trials from the inception of each database through May 2023. Methodological quality assessment was conducted by RoB 2.0, meta-analysis was conducted by RevMan 5.3 and Stata 15.1, and evidence quality was evaluated by GRADE. Moreover, reporting quality of acupuncture interventions was assessed using the Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA). Results: Thirty RCTs involving 2,220 patients were identified. We found that acupuncture was superior to conventional treatment (CT) in improving total responder rate [risk ratio (RR): 1.16, 95% confidence interval (CI): 1.09 to 1.25, p < 0.0001], decreasing constipation symptom scores [standardized mean difference (SMD): -0.65, 95% CI: -0.83 to -0.46, p < 0.00001], increasing serum P substance (SP) levels (SMD: 1.92, 95% CI: 0.47 to 3.36, p = 0.009), reducing the time to first bowel movement (BM) (SMD: -1.19, 95% CI: -2.13 to -0.25, p = 0.01), and lowing serum vasoactive intestinal peptide (VIP) levels (SMD: -2.11, 95% CI: -3.83 to -0.38, p = 0.02). Furthermore, acupuncture plus CT was superior regarding total responder rate (RR: 1.26, 95% CI: 1.17 to 1.35, p < 0.00001), serum SP levels (SMD: 2.00, 95% CI: 1.65-2.35, p < 0.00001), time to first BM (SMD: -2.08, 95% CI: -2.44 to -1.71, p < 0.00001), and serum VIP levels (SMD: -1.71, 95% CI: -2.24 to -1.18, p < 0.00001). However, regarding Bristol Stool Scale (BSS) score, acupuncture plus CT was superior to CT (SMD: -2.48, 95% CI: -3.22 to -1.73, p < 0.00001), while there was no statistically significant difference between acupuncture and CT (SMD: 0.28, 95% CI: -0.02 to 0.58, p = 0.07). Acupuncture causes fewer AEs than CT (RR: 0.13, 95% CI: 0.06 to 0.26, p < 0.00001), though there was no statistically significant difference between acupuncture plus CT vs. CT (RR: 1.30, 95% CI: 0.60 to 2.84, p = 0.51). Conclusion: Acupuncture may be an effective and safe therapy for PSC. However, given the inferior quality of clinical data, additional well-designed RCTs are required to confirm these findings.

A Review of The Application of Spectroscopy to Flavonoids from Medicine and Food Homology Materials.

Medicinal and food homology materials are a group of drugs in herbal medicine that have nutritional value and can be used as functional food, with great potential for development and application. Flavonoids are one of the major groups of components in pharmaceutical and food materials that have been found to possess a variety of biological activities and pharmacological effects. More and more analytical techniques are being used in the study of flavonoid components of medicinal and food homology materials. Compared to traditional analytical methods, spectroscopic analysis has the advantages of being rapid, economical and free of chemical waste. It is therefore widely used for the identification and analysis of herbal components. This paper reviews the application of spectroscopic techniques in the study of flavonoid components in medicinal and food homology materials, including structure determination, content determination, quality identification, interaction studies, and the corresponding chemometrics. This review may provide some reference and assistance for future studies on the flavonoid composition of other medicinal and food homology materials.

Semiquantitative assessment of 99mTc-MIBI uptake in parathyroids of secondary hyperparathyroidism patients with chronic renal failure.

Objective: To explore the valuably influential factors and improve the diagnostic accuracy and efficiency of 99mTc-methoxyisobutylisonitrile (MIBI) uptake in parathyroids of secondary hyperparathyroidism (SHPT) patients with chronic renal failure (CRF). Methods: The correlation analysis was performed between clinical indices related to CRF and 99mTc-MIBI uptake intensity TBR (the gray value mean ratio between the parathyroid target and the bilateral neck background, semiquantitatively calculated with ImageJ software). All clinical indices and TBRs were compared by a three- or two-level grouping method of MIBI uptake, which was visually qualitatively assessed. The three-level grouping method comprised slight, medium, and high groups with little, faint, and distinct MIBI concentration in parathyroids, respectively. The two-level grouping method comprised insignificant and significant groups with TBR greater than or less than 0.49-0.71, respectively. Results: MIBI uptake was significantly positively related to patient age, CRF course, hemodialysis vintage, serum parathyroid hormone (PTH), and alkaline phosphatase (AKP) but was significantly negatively related to serum uric acid (UA). MIBI washout was significantly positively related to patient age but was significantly negatively related to serum phosphorus (P) and calcium (Ca) × P. Oral administration of calcitriol and calcium could significantly reduce the MIBI uptake. MIBI uptake tendency might alter. Such seven indices, namely the MIBI uptake, CRF course, hemodialysis vintage, serum AKP, calcium, cysteine proteinase inhibitor C, and PTH, were comparable between the slight and medium groups but were significantly different between the slight and high groups or between the medium and high groups. The above seven indices plus blood urea nitrogen/creatinine were all significantly different between the insignificant and significant groups. All above significances were with P < 0.05. Conclusions: Patient age, CRF course, hemodialysis vintage, serum PTH, AKP, UA, phosphorus, Ca × P, oral administration of calcitriol and calcium, and parathyroids themselves can significantly influence MIBI uptake in parathyroids of SHPT patients with CRF. The two-level grouping method of MIBI intensity should be adopted to qualitatively diagnose the MIBI uptake.

Matrine induces autophagy in human neuroblastoma cells via blocking the AKT-mTOR pathway.

Neuroblastoma (NB) is one of the most common malignant solid tumors in children. Despite significant advances in the treatment strategy, the long-term survival rate of NB patients is only 50%. Developing new agents for NB patients deserves attention. Recent research indicates that matrine, a natural quinolizidine alkaloid component extracted from the traditional Chinese medicine Sophora root, is widely used for various diseases, including antitumor effects against a variety of cancers. However, the effect of matrine on NB is unknown. Herein, we found that matrine exerted antiproliferative activity in human NB cells in dose- and time-dependent manner. Matrine triggered autophagy in NB cells by blocking the AKT-mTOR signaling pathway and suppressing the phosphorylation of AKT and mTOR. 3-Methyladenine (3-MA), a PI3K inhibitor, protected against matrine-induced inhibition of cell proliferation, further supporting that the antitumor activity of matrine was at least partly autophagy-dependent. In vivo, matrine reduced tumor growth of SK-N-DZ cells in a dose-dependent manner. Matrine treatment significantly declined the phosphorylation of AKT and mTOR and enhanced the LC3 II/GAPDH ratio in NB xenografts. Altogether, our work uncovered the molecular mechanism underlying matrine-induced autophagy in NB and provided implications for matrine as a potential therapeutic agent against NB.

Abietane-Type Diterpenoids From Nepeta bracteata Benth. and Their Anti-Inflammatory Activity.

Terpenes possess a wide range of structural features and pharmaceutical activities and are promising for drug candidates. With the aim to find bioactive terpene molecules, eight new compounds were isolated from the medicinal plant Nepeta bracteata Benth., including seven new abietane-type diterpenoids (1-7), along with a new ursane-type triterpenoid (8). The structures of compounds 1-8 were elucidated through the detailed spectroscopic analyses of their 1D and 2D NMR and MS data, and the absolute configurations of compounds 1-7 were determined by comparing their experimental and calculated ECD spectra. Compound 1 was a novel degraded carbon diterpene with the disappearing of methyl signal at C-19, while compound 7 possessed a new norabietane-type diterpenoid carbon skeleton with the presence of five-membered lactone arising from ring rearrangement. The anti-inflammatory of all obtained isolates were evaluated on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and the results of anti-inflammatory activity screening showed that compared with the LPS model group, all compounds were significantly down-regulation the TNF-α inflammatory factor at the specific concentration, except for compound 6.

Severe clinical manifestation of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency associated with two novel mutations: a case report.

BACKGROUND: Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (mHS) deficiency is an autosomal recessive inborn error of metabolism, which will give rise to failure of ketogenesis in liver during illness or fasting. It is a very rare disease with only a few patients reported worldwide, most of which had a good prognosis after proper therapies. CASE PRESENTATION: We report a 9-month-old boy with mHS deficiency presenting with unusually severe and persistent acidosis after diarrhea and reduced oral food intake. The metabolic acidosis persisted even after supplementation with sugar and alkaline solution. Blood purification and assisted respiration alleviated symptoms, but a second onset induced by respiratory infection several days later led to multiple organ failure and death. Urine organic acid analysis during the acute episode revealed a complex pattern of ketogenic dicarboxylic and 3-hydroxydicarboxylic aciduria with prominent elevation of glutaric acid and adipic acid, which seem to be specific to mHS deficiency. Plasma acylcarnitine analysis revealed elevated 3-hydroxybutyrylcarnitine and acetylcarnitine. This is the first report of elevated 3-hydroxybutyrylcarnitine in mHS deficiency. Whole exome sequencing revealed a novel compound heterozygous mutation in HMGCS2 (c.100C > T and c.1465delA). CONCLUSION: This severe case suggests the need for patients with mHS deficiency to avoid recurrent illness because it can induce severe metabolic crisis, possibly leading to death. Such patients may also require special treatment, such as blood purification. Urine organic acid profile during the acute episode may give a hint to the disease.

Human umbilical cord-derived mesenchymal stem cells protect from hyperoxic lung injury by ameliorating aberrant elastin remodeling in the lung of O2-exposed newborn rat.

The incidence and mortality rates of bronchopulmonary dysplasia (BPD) remain very high. Therefore, novel therapies are imminently needed to improve the outcome of this disease. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) show promising therapeutic effects on oxygen-induced model of BPD. In our experiment, UC-MSCs were intratracheally delivered into the newborn rats exposed to hyperoxia, a well-established BPD model. This study demonstrated that UC-MSCs reduce elastin expression stimulated by 90% O2 in human lung fibroblasts-a (HLF-a), and inhibit HLF-a transdifferentiation into myofibroblasts. In addition, the therapeutic effects of UC-MSCs in neonatal rats with BPD, UC-MSCs could inhibit lung elastase activity and reduce aberrant elastin expression and deposition in the lung of BPD rats. Overall, this study suggested that UC-MSCs could ameliorate aberrant elastin expression in the lung of hyperoxia-induced BPD model which may be associated with suppressing increased TGFß1 activation.

[Effect of Lanthanum on accumulation of active constituent and key enzymes expression of Salvia miltiorrhiza hairy root].

The effect of Lanthanum on the accumulation of active constituent and key enzymes expression of Salvia miltiorrhiza hairy root were studied and furthermore signaling molecules mediating the synthesis of secondary metabolism was also defined in order to provide references for the reveal of synthesis mechanism of active constituent of S. miltiorrhiza hairy root inducing by Lanthanum. The content of active constituents were detected by HPLC. RNA was extracted with RNA prep Pure RNA purification kit (Tiangen). The results shows that LaCl3 processing promoted the accumulation of tanshinones and phenolic acids in S. miltiorrhiza hairy root. The accumulation of phenolic acids reached the highest at 9 d after treatment, and tanshinones accumulation continued to increase in 15 days. Accumulation of active substance in S. miltiorrhiza may relate with FPPS, TAT, HPPR several key enzyme activation.

[Study on Commercial Specification of Lonicerae Japonicae Flos].

OBJECTIVE: To provide the basis data for the institute of commercial specification standard of Lonicerae Japonicae Flos. METHODS: 39 samples of Lonicerae Japonicae Flos commercial of different grades in market were collected, and vernier caliper and electronic balance were used to measure the numbers of flower bud and blooming rate per 0. 5 g, contamination content, browning degree, milden and rot, length, upside diameter, middle diameter and bottom diameter of Lonicerae Japonicae Flos. The content of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, rutin, galuteolin,3,5-icaffeoylquinic acid and 4,5-dicaffeoylquinic acid were detected by HPLC. Correlation analysis, principal component analysis and cluster analysis were used by SPSS to analyze all index data,and the correlation of appearance characteristics and intrinsic active constituents was discussed. RESULTS: The numbers of flower bud and blooming rate per 0. 5 g, contamination content and browning degree were principal component indexes. The length of flower bud showed a significant correlation with galuteolin content, and the browning degree and upside diameter showed a significant correlation with chlorogenic acid content. CONCLUSION: Lonicerae Japonicae Flos commercial should be divided into four specification grades by sieved indexes.

[Effect of smoke water and distillation liquid on the seed germination and seedling growth of Trichosathes kirilowii].

Smoke water and distillation liquid were used to treat the seeds of Trichosathes kirilowii and to study the effects of smoke water and distillation liquid on the seed germination and seedling growth of T. kirilowii. The results showed that germination rate, germination index and germination vigor of T. kirilowii all were significantly improved with the treatment of SW and DL treatment. The activity of α-amylase were significantly increased with the treatment of SW and DL at 1:2,000. SW and DL treatment showed no significant effects on the activity of SOD. The activity of POD were markedly enhanced under the treatment of SW (1:000) and DL (1:2,000). CAT activity were increased with the treatment of SW and DL at 1:2,000 while were inhibited by SW and DL at 1:500. Seedling height and root length were increased with the treatment of SW and DL (1:1,000, 1:2,000). SW and DL treaments improved the content of chlorophyll, and moreover with the concentration of SW and DL, the stimulatory were also increased. This work demonstrated that smoke water and diatillation liquid at 1:2,000 could stimulate the seed germination and seedling growth of T. kirilowii, and it provided the references for the study of seed germination technology.

[Effects of plant-derived smoke water on accumulation of biomass and active substance of Salvia miltiorrhiza f. alba].

To study the effect of plant-derived smoke water on the accumulation of biomass and active substance of Salvia miltiorrhiza f. alba, seedlings of S. miltiorrhiza were treated with different concentrations of smoke water (1:500, 1: 1 000, 1: 2 000). The fresh weight and dry weight of underground part, the number of split-root, maximum root diameter, average root diameter, average root length, the content of lipophilic components and water-soluble components were measured. Results showed that fresh weight and dry weight of underground part were respectively improved by 98.01%, 44.32% and 85.71%, 28.57% with significant difference by smoke water treatment with concentration of 1: 500 and 1: 1 000. Maximum root diameter and dry weight of underground part were respectively enhanced by 58.44% and 85.71% by smoke water with concentration of 1:500. The content of tanshinone I and tanshinone II(A) were improved by smoke water treatment, however there were no significantly difference on the content of cryptotanshinone and dihydrotan shinone. This study indicates that smoke water treatment could be used to improve the accumulation of biomass and active substance content of S. miltiorrhiza f. alba, which could provide new ideas for its green cultivating.

[Comparison on surface ultrastructure characteristic and drought resistance of different Trichosanthes kirilowii strains].

Trichosanthes kirilowii has been widely cultivated as its medicinal use, health care and food value. Drought resistance of seedlings is an important feature in breeding. Seeds of two T. kirilowii strains were used to research the difference of surface ultrastructure characteristic and drought resistance. Scanning electron microscope was used to identify the surface ultrastructure characteristic of seeds and PEG was used to simulate drought stress. The seeds germination rate, MDA content, chlorophyll content and the antioxidant enzymes activity were measured under the drought stress. The results showed that the seed surface colour of KXY-001 was lighter than that of KXY-005. The testa cobwebbing of KXY-001 was more intensive than that of KXY-005. The germination rate of KXY-001 was higher than that of KXY-005 under drought stress. The MDA content was increased and the chlorophyll content was decreased with the increasing of drought degree. The SOD activity of KXY-001 was higher than that of KXY-005, while the activity of POD and CAT was also increased firstly and decreased later. Surface reticulate of seeds and hilar traits can be used as identification points to identify the investigated strains. SOD and POD are activated to resist drought in T. kirilowii seedlings and the drought resistance of KXY-001 is superior than that of KXY-005.

Farnesyltransferase inhibitor FTI-277 reduces mortality of septic mice along with improved bacterial clearance.

Treatment with statins, inhibitors of HMG-CoA reductase, extends the survival of septic mice. However, the molecular mechanisms underlying the cholesterol-lowering, independent beneficial effects of statins in sepsis are poorly understood. The inhibition of protein isoprenylation, namely farnesylation and geranylgeranylation, has been proposed as a mediator of the pleiotropic protective effects of statins, although direct evidence is lacking. Major features of sepsis-induced immune suppression include T-cell dysfunction, which is characterized by apoptosis of splenic T cells, increased CD4(+)Foxp3(+) regulatory T cells (Tregs), and suppression of type 1 helper T-cell response [e.g., interferon-γ (IFN-γ) secretion] in mice. Here, we show that the induction of sepsis by cecal ligation and puncture (CLP) resulted in increases in farnesyltransferase activity and farnesylated proteins in the spleen relative to sham operation. Treatment with farnesyltransferase inhibitor N-[4-[2(R)-amino-3-mercaptopropyl]amino-2-phenylbenzoyl]methionine methyl ester trifluoroacetate salt (FTI-277) (25 mg/kg b.wt. i.p.) at 2 h after CLP blocked the increase in farnesylated proteins and improved survival and bacterial clearance of septic mice. FTI-277 reverted to or mitigated sepsis-induced apoptosis in spleen and thymus, increased splenic CD4(+)Foxp3(+) Tregs, and suppressed IFN-γ secretion and proliferation of splenocytes in response to anti-CD3+CD28 antibodies in mice. Moreover, FTI-277 promoted macrophage phagocytotic activity in septic mice. These results indicate that elevation in protein farnesylation plays a role in derangements in immune function and mortality of septic mice. These findings suggest that prevention of immune dysfunction might contribute to FTI-277-induced improvement in survival of septic mice. These data highlight protein farnesyltransferase as a novel potential molecular target to reduce the mortality of patients with sepsis.

[Effects of nitrogenous phosphorus and potassium fertilizer on yield of Bupleurum scorzonerifolium].

OBJECTIVE: To study the effect of different fertilizer assortment (nitrogenous, phosphorus and potassium) on Bupleuram scorzonerifolium yield. METHODS: Three factors were designed by quadratic regression and D-optimum designation. RESULTS: As far as the biomass concerned, the best design of fertilizer was N 120. 3 - 333. 3 kg/hm(2) P2O5 0-939. 45 kg/hm(2), K2O 0 - 227. 25 kg/hm(2). As to R/T, the best design was N 62. 66 -333. 3 kg/hm(2), P2O5 0 -922. 54 kg/hm(2) , K2O 0 -227. 25 kg/hm(2). And for the root weight, the best design was N 34. 5 -333. 3 kg/hm(2), P2O5, 0 -939. 45 kg/hm2 , K2O 0-227. 25 kg/hm(2). CONCLUSION: Application quality of nitrogenous, phosphorus and potassium fertilizer are closely related with yield of B. Scorzonerifolium.