Antitussive Effect Research Articles

MXSGD alleviates CsA-induced hypoimmunity lung injury by regulating microflora metabolism.

Ma Xing Shi Gan Decoction (MXSGD) is a traditional remedy for treating lung injuries that was developed by the Typhoid and Fever School of Pharmaceutical Biology. It has antitussive and expectorant effects, anti-inflammatory, antiviral, regulates the body's immunity, etc. The aim of this study is to investigate whether MXSGD can ameliorate cyclosporine A (CsA)-induced hypoimmunity lung injury by regulating microflora metabolism. Methods: Establishment of a model for CsA-induced hypoimmunity lung injury. Using 16S rRNA high-throughput sequencing and LC-MS, the effects of MXSGD on gut flora and lung tissue microecology of mice with CsA-induced hypoimmunity were investigated. MXSGD was able to preserve lung tissue morphology and structure, reduce serum inflammatory marker expression and protect against CsA-induced lung tissue damage. Compared to the model, MXSGD increased beneficial gut bacteria: Eubacterium ventriosum group and Eubacterium nodatum group; decreased intestinal pathogens: Rikenellaceae RC9 intestinal group; reduced the abundance of Chryseobacterium and Acinetobacter, promoted the production of Lactobacillus and Streptococcus, and then promoted the lung flora to produce short-chain fatty acids. MXSGD was able to enhance the expression of serum metabolites such as Americine, 2-hydroxyhexadecanoylcarnitine, Emetine, All-trans-decaprenyl diphosphate, Biliverdin-IX-alpha, Hordatin A and N-demethyl mifepristone in the CsA-induced hypoimmunity lung injury model. MXSGD can restore gut and lung microbiota diversity and serum metabolite changes to inhibit inflammation, ameliorate CsA-induced hypoimmunity lung injury.

Medical Constituents of Ajwain (Trachyspermum ammi) for Human Benefits

Ajwain seed analysis has revealed it to contain fiber (11.9%), carbohydrates (38.6%), tannins, glycosides, moisture (8.9%), protein (15.4%), fat (18.1%), saponins, flavone and mineral matter (7.1%) containing calcium, phosphorous, iron and nicotinic acid. Ajwain fruits yield 2% to 4% brownish essential oil, with thymol as the major constituent (35% to 60%). The non-thymol fraction (thymene) contains para-cymene, γ-terpenine, α- and β-pinenes, dipentene, α-terpinene, and carvacrol. Minute amounts of camphene, myrcene, and α-3-carene also have been found in the plant. Alcoholic extracts contain a highly hygroscopic saponin. From the fruits, an yellow, crystalline flavone and a steroid-like substance has been isolated and it also contains 6-O-β-glucopyranosyloxythymol, glucoside and yields 25% oleoresin containing 12% volatile oil (thymol, γ-terpinene, para-cymene, and α- and β-pinene). The principal oil constituents of T. ammi are carvone (46%), limonene (38%), and dillapiole (9%). Ajwain is administered for curing stomach disorders, a paste of crushed fruits is applied externally for relieving colic pains; and a hot and dry fomentation of the fruits is applied on chest for asthma. Therapeutic uses of T. ammi fruits include; stomachic, carminative and expectorant, antiseptic and amoebiasis, antimicrobial. Seeds soaked in lemon juice with P runus amygdalus (badam) are given in curing amenhorroea and it is also used as antipyretic, febrifugal and in the treatment of typhoid fever. The antihypertensive effect of T. ammi administered intravenously in vivo, and the antispasmodic and bronchodilating actions in vitro showed that calcium channel blockade has been found to mediate the spasmolytic effects of plant materials and it is being considered that this mechanism contributed to their observed result and supported the traditional use of T. ammi in hyperactive disease states of the gut such as colic and diarrhea as well as in hypertension. Ajwain seeds revealed significant reduction of cough number which may be a result of its potent antitussive effect. The bronchodilatory effect of decocted extract of Ajwain on the asthmatic patients’ airways was examined in a subsequent trial study. According to the results, the extract has a relatively bronchodilatory effect on asthmatic airways compared to the effect of Theophylline at concentrations used. Ajwain was attributed to have diuretic and antilithiasis activity in ethnopharmacological reports. Accordingly, a human study was performed and in which, seeds of Ajwain were decocted in milk and given orally to volunteers suffering from urinary stone for a nine days period. The results were reported satisfactory against pure ca-oxalate stone. Another activity which has been proved for Ajwain is the antihyperlipidemic property. An in vivo study revealed that Ajwain seeds powder is extensively effective on lipid profile and can decrease total cholesterol, LDL-cholesterol, triglycerides and total lipids. Moreover, organic extract of seeds reduced atherogenic index and increased the level of HDL-cholesterol in albino rabbits. Ajwain was evaluated for the potentiality of antihypertensive and antispasmodic activity. In the related investigation, the aqueous-methanolic extract of the seeds caused a dose dependent decrease in arterial blood pressure in anaesthetized animal models. Furthermore, inhibitory effect on the K+-induced contractions was seen in isolated rabbit aorta and jejunum preparations during the application of Ajwain extract. These findings prove the potential antihypertensive and antispasmodic activity of Ajwain.

Discovery of antitussive material basis and mechanisms in Citri Sarcodactylis Fructus by coupling UHPLC-Q/Orbitrap HRMS combined spectrum-effect relationship and metabolomics analyses

Citri Sarcodactylis Fructus (CSF) is widely used as food raw material and traditional Chinese medicine. Fingerprints of different fractions of CSF were established for spectrum-effect relationship analysis, and the main compounds were identified by UHPLC Quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q/Orbitrap HRMS). The antitussive effect was evaluated using a classical mouse model of cough induced by ammonia water. One-way ANOVA was used to determine differences in efficacy. The potential active compounds were screened by spectrum-effect relationship with grey relational degree analysis (GRA), Pearson bivariate correlation analysis (Pearson's), and partial least squares analysis (PLS) analyses. Differential metabolites associated with cough in serum were screened and identified using orthogonal partial least squares-discriminant analysis, HMDB database, and UHPLC-Q/Orbitrap HRMS. Metabolic pathway analysis was performed using MetaboAnalyst 5.0. Results indicate that 70 % ethanol elution fraction (70 % EF) is the major active fraction, and 8 components were identified to possess antitussive effects. Metabolomic analysis showed that 19 metabolites are potential biomarkers related to cough, and 70 % EF can remarkable restore 13 of them to normal levels (P < 0.05). These biomarkers are mainly involved in glycerophospholipid metabolism and sphingolipid metabolism. This study aims to reveal the main pharmacodynamic active sites and potential active ingredients of CSF's antitussive effect. In addition, metabolomics was used to preliminarily elucidate the in-vivo regulatory mechanism of the antitussive effect of the 70 % EF of CSF.

Identification of the Bioactive Compounds of Raw and Honey-Processed Farfarae Flos by High-Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS) with the Spectrum-Effect Relationship and Chemometrics

Farfarae Flos (FF), also known as “Kuandonghua” in Chinese, is a commonly used traditional Chinese medicine (TCM) with various therapeutic properties, including antitussive, expectorant, antioxidant, and anti-inflammatory effects. Despite the widespread consumption of processed FF, there has been limited progress in improving quality control measures for both raw FF and honey-processed Farfarae Flos (PFF). This study aimed to establish a comprehensive strategy for quality evaluation and distinguish between FF and PFF by integrating high-performance liquid chromatography-mass spectrometry (HPLC-MS) analysis with chemometric techniques. Additionally, the antioxidant activities of FF and PFF were assessed using radical-scavenging experiments. The spectrum-effect relationship is the association of chemical composition information of the fingerprint with antioxidant activity, which was used to predict the primary active components that influence the antioxidant activity of FF. The results indicated that FF and PFF samples showed a clear distinction, and the most potent pharmacologically active ingredients were hyperoside, quercetin, caffeic acid, isoquercitrin, neochlorogenic acid, rutin, cryptochlorogenic acid, and isochlorogenic acid C. Moreover, the comprehensive efficacy of the honey-processed FF was better than for raw FF. In conclusion, the findings of this study provide a scientific foundation for future evaluation of the quality, further research, and practical use of FF herbs.

A strategy for deciphering the bioactive metabolites of Farfarae Flos by the inter-individual variability of the antitussive effect

Farfarae Flos is a commonly used traditional herb for the treatment of respiratory disorders. In this study, ultra-high-performance liquid chromatography coupled with time-of-flight mass spectrometry combined with the mass defect filter method was used for the qualitative analysis of Farfarae Flos metabolites in the lung tissues. Then a method for the simultaneous determination of 14 Farfarae Flos metabolites was developed and validated in terms of specificity, linearity, precision and accuracy, matrix effect and recovery. The method was applied to compare the lung tissue of Farfarae Flos treated mice, and 10 caffeoylquinic acid metabolites were higher in the mice with better antitussive effect. Further network pharmacology analysis and molecular docking results showed that these metabolites played an important role in the antitussive effect of Farfarae Flos. This study presented a novel strategy for deciphering the active compounds of herbal medicine by inter-individual variability of bioactivities.

Chemical Space of Small Molecule Exploration for the Elucidation of Cough Suppressant Pharmacology of Ying Su Ke/Zi

IntroductionChronic cough, a prevalent condition, lacks effective medical solutions. Traditionally, Ying Su Ke/Zi (derived from Papaver somniferum L.) has been used in certain ethnic herbal formulas to address cough. However, there is a notable absence of molecular-level exploration regarding their mechanism for treating cough. MethodsStarting with the chemical ingredients of Ying Su Ke/Zi, this study used principal component analysis to explore the chemical space of these compounds and set four rounds of screening criteria based on the chemical space distribution to quickly identify active compounds. Following that, their targets were predicted using the weighted ensemble system model, and target enrichment analysis was executed. ResultsIn total, 247 compounds in Ying Su Ke/Zi were data-mined from literature reports, based on which four rounds of screening yielded 88 potential active chemicals, mostly alkaloids. Besides, 168 target proteins, mostly G-protein-coupled receptors, were identified, and meanwhile the results of the enrichment analysis revealed that these target proteins are, mostly, localised at cell membranes, cell junctions, and cell projections, and they were primarily involved in biological processes ranging from stimulus response, signalling, and bioregulation, possessing molecular functions concerning altering molecular transduction activity and binding. Moreover, the key biological pathways covered by these target proteins are neuroactive receptor-ligand interaction pathway, serotonergic synapse pathway, etc. ConclusionsIntegrating the foregoing findings with the pathophysiological characteristics of cough, the current study reveals that Ying Su Ke/Zi exert their antitussive pharmacological effects primarily via opioidergic and serotonergic mechanisms.

In vitro anti-severe acute respiratory syndrome coronavirus 2 effect of Ephedra przewalskii Stapf extract

Ethnopharmacological relevanceThe terrestrial stems of Ephedra (Ephedra spp.; including Ephedra sinica Stapf and Ephedra przewalskii Stapf) extracts are used in traditional medicines in East Asia. In Japan, the Kampo formula containing E. sinica extract is prescribed for the treatment of the common cold, influenza virus infections, and mild symptoms of coronavirus disease 2019 (COVID-19). Although ephedrine alkaloids in E. sinica exert antitussive effects, they may have side effects associated with the sympathetic nervous system. E. przewalskii extract, a drug used in traditional Uyghur and Mongolian medicine, is considered to be free of ephedrine alkaloids and is a promising candidate for the treatment of infectious diseases. However, its use is currently limited because evidence of its antiviral efficacy remains inconclusive.Aim of the study: We compared the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) effects of E. przewalskii and E. sinica extracts in vitro. Additionally, we examined the differences in their antiviral effects against different SARS-CoV-2 strains. Materials and methodsVeroE6/TMPRSS2 cells were infected with SARS-CoV-2 (Conventional, Delta, and Omicron strains—BA.1, BA.2, BA.4, and BA.5), and lysates prepared from each herbal extract were added. The infectious titer was determined using the 50% tissue culture infectious dose (TCID50) method; in turn, the half-maximal inhibitory concentration (IC50) was calculated for each extract to compare the antiviral efficacy of E. sinica and E. przewalskii extracts. Further, the extracts were compared with remdesivir for their antiviral efficacy against the conventional viral strain. To verify the effect of the inactivation of virus particles, these extracts were added to each SARS-CoV-2 strain, and the infectious titers were determined using the TCID50 method. ResultsThe antiviral efficacy (i.e., IC50) of the E. przewalskii extract against each SARS-CoV-2 strain was 2.7–10.8-fold greater than that of the E. sinica extract. The antiviral efficacy of the E. przewalskii extract against conventional viral strains was compared with that of remdesivir, which was 1/27.6 of remdesivir's efficacy. The E. sinica extract showed minimal inactivation of virus particles of each strain, whereas the E. przewalskii extract resulted in substantial viral inactivation. ConclusionsThe E. przewalskii extract showed higher antiviral activity against SARS-CoV-2 than the E. sinica extract. Overall, our study suggests that E. przewalskii extract can be used for the treatment of viral infections, including COVID-19.

Liquiritin targeting Th17 cells differentiation and abnormal proliferation of keratinocytes alleviates psoriasis via NF-κB and AP-1 pathway.

Psoriasis is a common immune-mediated inflammatory skin disease, caused by disturbed interactions between keratinocytes and immune cells. Chinese medicine shows potential clinical application for its treatment. Liquiritin is a flavone compound extracted from licorice and shows potential antitussive, antioxidant and antiinflammatory effects, and therefore may have potential as a psoriasis therapeutic. The aim of this work was to examine the possible roles that liquiritin may have in treating psoriasis. HaCaT cells were stimulated by TNF-α with or without liquiritin, harvested for analysis by western blots and RT-qPCR, and the cellular supernatants were collected and analyzed by ELISA for cytokines. In addition, 4 groups of mice were examined: Normal, Vehicle, LQ-L and LQ-H. The mice were sacrificed after 6 days and analyzed using IHC, ELISA, RT-qPCR and flow cytometry. The results showed that liquiritin could significantly inhibit the progression of psoriasis both in vitro and in vivo. Liquiritin strongly suppressed the proliferation of HaCaT keratinocytes but did not affect cell viability. Moreover, liquiritin alleviated imiquimod-induced psoriasis-like skin inflammation and accumulation of Th17 cells and DCs in vivo. In TNF-α-induced HaCaT keratinocytes, both protein and mRNA expression levels of inflammatory cytokines were sharply decreased. In imiquimod-induced mice, the activation of NF-κB and AP-1 was reduced after treatment with liquiritin. Collectively, our results show that liquiritin might act as a pivotal regulator of psoriasis via modulating NF-κB and AP-1 signal pathways.

A Review of the Magical Indian Shrub Asparagus Racemosus

Asparagus racemosus a climbing Ayurvedic plant which is most an important medicinal plant of tropical and subtropical India. The name “Shatavari” means “a woman who possess 100 children”, referring to the shatavari rejuvenation effect in female reproductive organs.. Aromatic and medicinal plants have played significant role in the lives of humans by providing products for both food and medicine. Shatavari has been described to use as antioxidant, immune stimulant, and anti tussive effects. It is also very useful and effective in the treatment of cancer, kidney disorder, chronic fevers, ulcers, chronic fevers etc. Main use of this drug is in female disorders and several menstrual disorders. The present article explores the taxonomy, morphology, cultivation, harvesting and biological properties of A. racemosus.

Gabapentin alleviated the cough hypersensitivity and neurogenic inflammation in a guinea pig model with repeated intra-esophageal acid perfusion

ObjectiveThe anti-tussive effect of gabapentin and its underlying neuromodulatory mechanism were investigated via a modified guinea pig model of gastroesophageal reflux-related cough (GERC). MethodsIntra-esophageal perfusion with hydrochloric acid (HCl) was performed every other day 12 times to establish the GERC model. High-dose gabapentin (48 mg/kg), low-dose gabapentin (8 mg/kg), or saline was orally administered for 2 weeks after modeling. Cough sensitivity, airway inflammation, lung and esophagus histology, levels of substance P (SP), and neurokinin-1 (NK1)-receptors were monitored. ResultsRepeated intra-esophageal acid perfusion aggravated the cough sensitivity in guinea pigs in a time-dependent manner. The number of cough events was significantly increased after 12 times HCl perfusion, and the hypersensitivity period was maintained for 2 weeks. The SP levels in BALF, trachea, lung, distal esophagus, and vagal ganglia were increased in guinea pigs receiving HCl perfusion. The intensity of cough hypersensitivity in the GERC model was significantly correlated with increased SP expression in the airways. Both high and low doses of gabapentin administration could reduce cough hypersensitivity exposed to HCl perfusion, attenuate airway inflammatory damage, and inhibit neurogenic inflammation by reducing SP expression from the airway and vagal ganglia. ConclusionsGabapentin can desensitize the cough sensitivity in the GERC model of guinea pig. The anti-tussive effect is associated with the alleviated peripheral neurogenic inflammation as reflected in the decreased level of SP.

Anti-inflammatory, anti-tussive effects and toxicity evaluation of Qingfei Dayuan granules.

To study the anti-inflammatory and anti-tussive effects of Qingfei Dayuan granules (, QFDY), and to evaluate the acute and sub-chronic toxicity of QFDY. Anti-inflammatory effects were evaluated by murine model of xylene induced ear edema in mice. Ear swelling degree was calculated and tumor necrosis factor-α, interleukin-1β and interleukin-6 were determined. Anti-tussive evaluations were carried out in the mouse cough model induced by ammonia liquor. Latent period cough and number of cough within 3 min were counted. In acute toxicity study, the rats were randomly divided into test group and solvent control group. Body weighs, food intakes and general clinical signs were monitored. In the sub-chronic toxicity study, QFDY was administered to rats at 0, 4, 8 and 16 g/kg per day for 28 and 30 d of post treatment was conducted. Mortalities, clinical signs, body weight changes, food intakes, ophthalmological examinations, hematological parameters, biochemical indicators, electrolyte indicators, urinalyses and histopathological examinations were monitored. QFDY significantly inhibited the development of ear edema in anti-inflammatory assay and decreased cough frequency caused by ammonia liquor. The results presented a dose-effect relationship. In acute toxicity study, no abnormality exhibited at dose of 24.0 g/kg per day during the 14-d observation period. In the sub-chronic toxicity study, higher reticulocyte count, lymphocyte and lower Cl-, blood urea nitrogen were analyzed compared with the solvent control group. But the differences were considered to be incidental and not clinically toxic. Obvious dose-effect relationship of urine color was observed, and the three test groups at the end of the experiments resulted in significant increase in urobilinogen, bilirubin, ketone body and urine leukocyte. However, all the positive indicators returned to normal in the recovery period. Therefore, no toxicological changes were found during the study period. QFDY showed significant anti-inflammatory and anti-tussive effects in mice. The lethal dose (LD50) of per oral QFDY in rats was estimated to be more than 24.0 g/kg per day and the no observed adverse effect level was over 16 g/kg per day, which suggested that QFDY is relatively safe for oral medication at the present dose on rats. Our experimental results provide a reference for the further development and research of QFDY.

Chronic cough relief by allosteric modulation of P2X3 without taste disturbance

P2X receptors are cation channels that sense extracellular ATP. Many therapeutic candidates targeting P2X receptors have begun clinical trials or acquired approval for the treatment of refractory chronic cough (RCC) and other disorders. However, the present negative allosteric modulation of P2X receptors is primarily limited to the central pocket or the site below the left flipper domain. Here, we uncover a mechanism of allosteric regulation of P2X3 in the inner pocket of the head domain (IP-HD), and show that the antitussive effects of quercetin and PSFL2915 (our nM-affinity P2X3 inhibitor optimized based on quercetin) on male mice and guinea pigs were achieved by preventing allosteric changes of IP-HD in P2X3. While being therapeutically comparable to the newly licensed P2X3 RCC drug gefapixant, quercetin and PSFL2915 do not have an adverse effect on taste as gefapixant does. Thus, allosteric modulation of P2X3 via IP-HD may be a druggable strategy to alleviate RCC.

Identification of a New Pyrrolyl Pyridoindole Alkaloid, Melpyrrole, and Flazin from Honey and Their Cough-Suppressing Effect in Guinea Pigs.

The cough-suppressing effect of honey was demonstrated for the first time using a guinea pig model whereby cough was induced by citric acid and capsaicin, and a new pyrrolyl pyridoindole, 1-(5-(hydroxymethyl)-1H-pyrrol-2-yl)-9H-pyrido[3,4-b]indole-3-carboxylic acid (1), named melpyrrole, and flazin (2) were identified as the active principle components. The structures of 1 and 2 were estimated using a combination approach of an activity-guided survey and LC-MS/MS multivariate analysis and were finally established by total synthesis of 1 and comparison with an authentic standard for 2. Both compounds showed antitussive activity comparable to that of dextromethorphan in guinea pigs. Their antitussive effects were unaffected by an opioid antagonist and reversed by a nitric oxide (NO) synthase inhibitor, indicating that these natural products do not act directly on opiate receptors but through the NO signaling pathway.

Evaluation of Antitussive, Expectorant and Analgesic Activities of Aqueous Extracts of Di-herbal Formulation of Whole Plant of Euphobia hirta and Lactuca virosa Leaf on Rodents

Euphorbia hirta and lactuca virosa are used to treat various ailment traditionally. This study aims at evaluating the antitussive, expectorant and analgesic effects of aqueous extracts of di-herbal formulation of Euphobia hirta and Lactuca virosa leaf. Citric acid induced, ammonia induced cough and phenol red dye secretion models were used. Hot plate and acetic acid induced writhing were used for analgesia. Combined 100mg/kg Euphorbia hirta and 50mg/kg lactuca virosa, 100mg/kg Euphorbia hirta and 100mg/kg lactuca virosa, 100mg/kg lactuca virosa only and 25 mg/kg of codeine phosphate reduces the number of cough bouts in the citric acid induced cough (P&lt;0.05) compared to control. Combined 50mg/kg Euphorbia hirta and 100mg/kg lactuca virosa,100mg/kg Euphorbia hirta, 100mg/kg lactuca virosa and codeine phosphate reduces the number of cough bouts in the ammonia induced cough (P&lt;0.001; P&lt;0.0001) compared to the control. Combined 50mg/kg Euphorbia hirta and 100mg/kg lactuca virosa, 100mg/kg Euphorbia hirta and 50mg/kg lactuca virosa, 100mg/kg Euphorbia hirta and 100mg/kg lactuca virosa and 15mg/kg of Bromo-hexane increases the secretion of dye (P&lt;0.0001; p&lt;0.05) compared to control in phenol red dye secretion in mice. 100mg/kg Euphorbia hirta and 50mg/kg lactuca virosa,100mg/kg of Euphorbia hirta and 100mg/kg lactuca virosa and 3mg/kg Pentazocin increases the latency of pain threshold of mice (P&lt;0.05). All the doses of the extract including 3mg/kg pentazocin increases the latency to pain threshold in the mice (P&lt;0.001) after 2 hours. All the doses of the extract including aspirin reduces number of writhing (P&lt;0.01). Euphorbia hirta and lactuca virosa has antitussive, expectorant and analgesic properties.

Optimal compatibility proportional screening of Trichosanthis Pericarpium - Trichosanthis Radix and its anti - Inflammatory components effect on experimental zebrafish and coughing mice

Ethnopharmacological relevanceThe herbal pair of Trichosanthis Pericarpium (TP) - Trichosanthis Radix (TR) can be seen in the famous formula “Beimu Gualou San”. It is a commonly selected combination of medicinal herbs for the treatment of cough with lung heat. Both drugs are derived from Trichosanthes kirilowii Maxim, a medicinal plant known for its ability to clear heat, resolve phlegm, produce saliva, and alleviate dryness. However, the optimal combination ratio and active ingredients of TP-TR have yet to be determined. Aim of the studyThis study aims to investigate the optimal combination ratio of TP-TR and its anti-inflammatory active ingredients in cough treatment. Materials and methodsA zebrafish (Danio rerio) inflammatory injury model and response surface method were applied in the present study to determine the appropriate proportion of TP-TR. Chemical constituents in TP-TR were identified using HPLC-ELSD and UPLC-MS/MS methods. Subsequently, a cough mouse model was created using an ammonia solution to evaluate the effectiveness of the optimal TP-TR ratio. Network pharmacology and intestinal flora sequencing were used to validate the anti-inflammatory components of TP-TR. ResultsThe herbal pair of TP - TR at the ratio of 1:2 showed an optimal anti-inflammatory effect, with a composite inflammatory factor score of 119.645 in the zebrafish experiment. TP-TR combination facilitated the dissolution of glutamine, inosine, cytosine, isoquercetin, and other substances. In the animal model, the TP-TR (1:2) treatment significantly reduced the frequency of coughs and prolonged cough latency compared to the model group. Results of the network pharmacology indicated that inflammatory-related factors such as TLR4, STAT3, EGFR, and AKT1 played crucial roles in cough treatment with TP-TR, consistent with the validation experiment. The 16s rDNA sequencing results revealed a significant increase in the abundance of Clostridia_UCG-014, Lachnospiraceae, Christenella, Ruminococcus, and other species in the intestinal tract of mice after modelling. TP-TR (1:2) reduced the abundance of pro-inflammatory flora such as Clostridium_UCG-014 and Lachnospira, which were closely associated with L-lysine and trans-4-hydroxy-L-proline present in TP-TR according to correlation analysis. ConclusionTP-TR may promote the dissolution of glutamine, thymidine, inosine, cytosine, isoquercetin, and other components through their combination, thereby regulating the abundance of Clostridium_UCG-014 and Lachnospira and exerting an antitussive effect. This study, for the first time, showed that TP-TR at a 1:2 ratio exhibits superior anti-inflammatory effects. In addition to inflammatory mediators like EGFR, TLR4, AKT1, and STAT3, gut microbes could also serve as potential regulatory targets of TP-TR in the treatment of cough. 2'-Deoxyguanosine monohydrate, L-lysine, L-leucine, γ-aminobutyric acid, L-valine, L-tryptophan, L-proline, trans-4-hydroxy-L-proline, L-methionine, uridine, 2'-deoxyinosine, guanosine, cucurbitacin B and cucurbitacin D were identified as its anti-inflammatory active ingredients.

Relaxant effect of thymol on smooth muscle

Thymol is a phenolic monoterpene with colorless crystalline shapes or white crystalline powder with a spicy, caucasian and sweet taste. Its chemical structure is characterized by a hydroxyl group (-OH) attached to a benzene ring. It provides for the hydroxylation of P-cymine along with its carvacrol’s isomer. In this molecule different therapeutic properties have been registered in this molecule, such as spasmolytic, anticancer, anti-inflammatory, fungicidal, antibacterial, antioxidant and hepatoprotective. This monoterpene is found in different species of the genus Thymus, especially T. Vulgaris and T. zigis with a percentage that fluctuates between 10% and 60% found in the aerial part of both plants, likewise, it is also found in Lagoecia cuminoides between a 73% and 95% and in Trachyspermum copticum between 37.2 and 72.3% in the seed and fruits of this plant. Studies on its beneficial effects on health have been carried out in different species, highlighting rats, mice, rabbits, guinea pigs, chickens, human cell lines; distinguishing human studies have been conducted 3 studies to decrease the effects of asthma, antitussive and anti-inflammatory effect on the lungs. The aim of this narrative article is to describe the processes of contraction and relaxation of smooth muscle and the spasmolytic effect of thymol in different smooth muscle tissues in rats, mice, guinea pigs and rabbits. Through this research, it is suggested to the scientific community to study the possible mechanisms of action of this molecule in the different types of smooth muscle tissue for subsequent clinical studies

Extraction of rutin from tagetes erecta (Marigold) and preparation of peroral nano-suspension for effective antitussive/expectorant therapy

The present study narrates the extraction of rutin from Tagetes erecta (Marigold) via maceration followed by ultrasonication. The extracted rutin was further fabricated into nanoparticles by high-pressure homogenization (HPH) and assessed by HPLC, DSC, XRD, TEM, and FTIR spectroscopy. The optimized batch of nanoparticles obtained using 32 central composite design (CCD) which exhibited particle size 209±14 nm, PDI 0.234±0.06, and 92±1.3% entrapment efficiency. The lyophilized rutin nanoparticles were further converted into nano-suspension. Interestingly, the rutin nano-suspension exhibited a similar antitussive effect in vivo as that by standard treatment pentoxyverine and reduced the coughing times within 2 min. Also, the phlegm showed high UV absorbance, implying its better expectorant activity than the standard and control. The rutin nano-suspension was highly stable and shelf life was found to be ∼29.1 months. The present study, for the first time, paves a way for the use of rutin nano-suspension to overcome chest congestion, shortening of breath, and in the management of cough.

Effect of saffron, black seed, and their main constituents on inflammatory cytokine response (mainly TNF-α) and oxidative stress status: an aspect on pharmacological insights.

Tumor necrosis factor-α(TNF-α), an inflammatory cytokine, is produced by monocytes and macrophages. It is known as a 'double-edged sword' because it is responsible for advantageous and disadvantageous events in the body system. The unfavorable incident includes inflammation, which induces some diseases such as rheumatoid arthritis, obesity, cancer, and diabetes. Many medicinal plants have been found to prevent inflammation, such as saffron (Crocus sativus L.) and black seed (Nigella sativa). Therefore, the purpose of this review was to assess the pharmacological effects of saffron and black seed on TNF-α and diseases related to its imbalance. Different databases without time limitations were investigated up to 2022, including PubMed, Scopus, Medline, and Web of Science. All the original articles (in vitro, in vivo, and clinical studies) were collected on the effects of black seed and saffron on TNF-α. Black seed and saffron have therapeutic effects against many disorders, such as hepatotoxicity, cancer, ischemia, and non-alcoholic fatty liver, by decreasing TNF-α levels based on their anti-inflammatory, anticancer, and antioxidant properties. Saffron and black seed can treat a variety of diseases by suppressing TNF-α and exhibiting a variety of activities such as neuroprotective, gastroprotective, immunomodulatory, antimicrobial, analgesic, antitussive, bronchodilator, antidiabetic activity, anticancer, and antioxidant effects. To uncover the beneficial underlying mechanisms of black seed and saffron, more clinical trials and phytochemical research are required. Also, these two plants affect other inflammatory cytokines, hormones, and enzymes, implying that they could be used to treat a variety of diseases.

Clinical effect of wumei bolus on ulcerative colitis: A meta-analysis

Wumei Bolus is a traditional Chinese medicine prescription, first appeared in Shennong Bencao Jing. Modern pharmacology believes that Wumei Bolus has antibacterial, antitussive, sedative, antiviral and anti-tumor effects, and plays a therapeutic role by acting on multi-target/multi-pathway. Moreover, it has great advantages in digestive system diseases, such as repairing the damaged gastrointestinal mucosa and improving the inflammatory environment. Aim of the studyThis review aimed to evaluate the efficacy and safety of prescriptions based on the Wumei Bolus treating ulcerative colitis (UC). Materials and methodsIn this meta-analysis, we searched CNKI, Wanfang Database, VIP, Pubmed, Web of Science (WOS) with language restrictions of Chinese and English for articles published from the establishment of the database to Dec 2022. This meta-analysis controlled randomized controlled trials (RCTs) assessing the efficacy and safety of Wumei Bolus against ulcerative colitis and using RevMan 5.4 and Stata 15.0to analyze information from the compliant studies. ResultsThe search incorporated 3145 results (1617 cases assigned into Wumei Bolus group and 1528 cases assigned into control group), from which 37 studies fulfilled our inclusion criteria and were included. The outcomes of this meta-analysis showed that compared to the control group, the Experiment group was significantly more effective (RR = 1.24，95%CI [1.20，1.28])and lower adverse reactions (RR = 0.32, 95%CI [0.20, 0.53]). According to the subgroup analysis, The results showed that the RR = 1.23 and 95%CI [1.16, 1.30] in the group treated with Wumei Bolus alone and the group treated with Western medicine with RR = 1.25 and 95%CI [1.20, 1.30], indicating that the efficacy of Wumei Bolus in the treatment of UC was better and the difference was statistically significant (P < 0.00001). The results showed that compared with the control group, the experimental group had more advantages in reducing inflammatory factors whether TNF-α or IL-8 (TNF-α:SMD = −4.44, 95%CI [-5.75, −3.14]; IL-8: SMD = −3.02, 95%CI [-4.06, −1.97]) and improving TCM symptoms and reduced TCM syndrome points (SMD = −3.82, 95%CI [-4.30, −3.34]). There was significant association of the basic treatment of Wumei Bolus improving clinical efficacy, reducing serum pro-inflammatory factors, improving symptoms, and reducing adverse reactions in UC patients. These results were statistically significant (P < 0.00001). ConclusionsThe prescriptions based on the Wumei Bolus is greatly related to reducing serum pro-inflammatory factors, improving symptoms, improving clinical efficacy and reducing adverse reactions in the treatment of UC compared to conventional western medicine and improve the total clinical effective rate.

The activities and mechanisms of intestinal microbiota metabolites of TCM herbal ingredients could be illustrated by a strategy integrating spectrum-effects, network pharmacology, metabolomics and molecular docking analysis: Platycodin D as an example

BackgroundThe intestinal microbiota plays a key role in understanding the mechanism of traditional Chinese medicine (TCM), as it could transform the herbal ingredients to metabolites with higher bioavailability and activity comparing to their prototypes. Nevertheless, the study of the activity and mechanism of microbiota metabolites reported by the published literature still lacks viable ways. Hence a new strategy is proposed to solve this issue. PurposeA new strategy to study the activity and mechanism of intestinal microbiota metabolites of TCM herbal ingredients by integrating spectrum-effect relationship, network pharmacology, metabolomics analysis and molecular docking together was developed and proposed. MethodPlatycodin D (PD) and its microbiota metabolites with antitussive and expectorant effect were selected as an example for demonstration. First, the PD and its microbiota metabolites with important contribution to antitussive and/or expectorant effects were screened through spectrum-effect relationship analysis. Second, network pharmacology and metabolomics analysis were integrated to identify the upstream key targets of PD and its microbiota metabolites as well as the downstream endogenous metabolites. Finally, the active forms of PD were further confirmed by molecular docking. ResultsResults showed that PD was an active ingredient with antitussive and/or expectorant effects, and the active forms of PD were its microbiota metabolites: 3-O-β-d-glucopyranosyl platycodigenin, 3-O-β-d-glucopyranosyl isoplatycodigenin, 7‑hydroxyl-3-O-β-d-glucopyranosyl platycodigenin, platycodigenin and isoplatycodigenin. In addition, those microbiota metabolites could bind the key targets of PAH, PLA2G2A, ALOX5, CYP2C9 and CYP2D6 to exert antitussive effects by regulating four metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, glycerophospholipid metabolism and linoleic acid metabolism. Similarly, they could also bind the key targets of PLA2G1B, ALOX5, CYP2C9 and CYP2D6 to exert expectorant effect by regulating two pathways of glycerophospholipid metabolism and linoleic acid metabolism. ConclusionThe proposed strategy paves a new way for the illustration of the activities and mechanisms of TCM herbal ingredients, which is very important to reconcile the conundrums of TCM herbal ingredients with low oral bioavailability but high activity.