1.Therapeutic effect of Leonuri Herba aqueous decoction on primary dysmenorrhea in rats and its metabolomic analysis.
Liu-Jun WU ; Yan CHEN ; Zi-Wei LIN ; Chen SUN ; Liang XIONG ; Xiao-Fang XIE ; Cheng PENG
China Journal of Chinese Materia Medica 2023;48(22):6093-6106
This study aimed to investigate the therapeutic effect of Leonuri Herba aqueous decoction on primary dysmenorrhea(PD) and explore the underlying mechanism in conjunction with untargeted metabolomics. Forty adult female rats were randomly divi-ded into a normal group, a model control group, ibuprofen(0.12 g·kg~(-1)) group, and high-and low-dose Leonuri Herba aqueous decoction(5 and 2.5 g·kg~(-1)) groups, with eight rats in each group. The PD rat model was prepared using intramuscular injection of estradiol benzoate combined with intraperitoneal injection of pitocin. Drugs were administered by gavage from the 4th day of modeling for 7 d. After the last administration, pitocin was injected intraperitoneally, and the writhing latency and writhing times within 30 min were recorded. The uterine and ovarian coefficients were determined. Estradiol(E_2), progesterone(Prog), oxytocin(OT), cyclooxyge-nase 2(COX-2), prostaglandin E_2(PGE_2), prostaglandin F_(2α)(PGF_(2α)), and Ca~(2+) levels in uterine tissues were measured by ELISA and biochemical kits. Morphological changes in uterine and ovarian tissues were observed by hematoxylin-eosin(HE) staining. The protein expression of oxytocin receptor(OTR), prostaglandin E_2 receptor 3(EP3), and estrogen receptor alpha(ERα) in uterine tissues was detected by immunohistochemistry. The mRNA expression of OTR, PGE_2 receptors 1-4(EP1, EP2, EP3, and EP4), and PGF_(2α) receptor(FP) in uterine tissues was detected by quantitative real-time PCR. Untargeted metabolomics analysis was performed by ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(LC-QTOF-MS) technology to screen potential biomarkers and enrich metabolic pathways. The results showed that Leonuri Herba was able to significantly reduce the writhing times in PD rats(P<0.05 or P<0.01), significantly reduce the uterine and ovarian coefficients(P<0.01), and improve their histomorphology. After treatment with Leonuri Herba, PGE_2 content was significantly increased(P<0.05), COX-2, PGF_(2α) and Ca~(2+) content, and PGF_(2α)/PGE_2 was significantly decreased(P<0.05 or P<0.01), and OT content was decreased, while E_2 and Prog content tended to further increase in uterine tissues of PD rats. Correspondingly, OTR and EP3 protein expression was significantly downregulated(P<0.05 or P<0.01) and ERα protein expression was upregulated(P<0.05) in uterine tissues. The mRNA expression of FP and EP4 in uterine tissues was significantly downregulated(P<0.01), and the mRNA expression of EP1, EP3, and OTR showed a decreasing trend. The untargeted metabolomics results showed that 10 differential metabolites were restored in the plasma of PD rats after Leonuri Herba treatment. The results indicate that Leonuri Herba is effective in the prevention and treatment of PD, and the underlying mechanism may be attributed to the regulation of PGs synthesis and corresponding receptor binding.
Humans
;
Rats
;
Female
;
Animals
;
Estrogen Receptor alpha
;
Oxytocin
;
Dysmenorrhea/metabolism*
;
Cyclooxygenase 2
;
Dinoprostone
;
RNA, Messenger/metabolism*
;
Dinoprost
2.Effects of electroacupuncture on NLRP3 inflammasome and pyroptosis protein GSDMD in uterine tissue in rats with primary dysmenorrhea.
Shao-Hua WANG ; Yu LIU ; Xiao XUE ; Si-An PAN ; Han-Yu YUAN ; Juan LI ; Zeng-Hui YUE
Chinese Acupuncture & Moxibustion 2023;43(3):309-316
OBJECTIVE:
To observe the effects of electroacupuncture (EA) on NLRP3 inflammasome and its downstream protein gastermin D (GSDMD) in rats with primary dysmenorrhea (PDM), and to explore the potential mechanism of EA on the treatment of PDM.
METHODS:
Forty healthy female SD rats without pregnancy were randomly divided into a control group, a model group, an EA group and an ibuprofen group, 10 rats in each group. PDM model was prepared by injection of estradiol benzoate and oxytocin. Except the control group, the rats in each group were subcutaneously injected with estradiol benzoate for 10 days, and oxytocin was injected on the 11th day. The rats in the EA group were intervened with EA (dense wave, frequency of 50 Hz) at "Guanyuan" (CV 4) and "Sanyinjiao" (SP 6) at the same time of modeling, once a day, 20 min each time, for 10 consecutive days. The rats in the ibuprofen group were treated with 0.8 mL of ibuprofen by gavage (concentration of ibuprofen solution was 1.25 mg/mL) for 10 consecutive days. After modeling, the writhing reaction was observed. After intervention, the HE staining method was used to observe the histological morphology of uterus and evaluate the pathological damage score of uterus; ELISA method was used to detect the serum levels of prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α); Western blot method was used to detect the protein expression of NLRP3, apoptosis related spot like protein (ASC), caspase-1, GSDMD, GSDMD-N and inflammatory factors (interleukin [IL]-1β, IL-18) in uterine tissue.
RESULTS:
In the model group, a large number of vacuolar degeneration and death of endometrial epithelial cells, spiral arterioles congestion in lamina propria and neutrophil infiltration were observed. In the EA group, there was a small amount of vacuolar degeneration and death of endometrial epithelial cells, a small amount of spiral arterioles congestion in the lamina propria, and a small amount of neutrophils infiltration. In the ibuprofen group, there was very small number of degeneration and death of endometrial epithelial cells, and no obvious arterial congestion was found in lamina propria, and neutrophil infiltration was occasionally seen. Compared with the control group, in the model group the number of writhing was increased (P<0.01), the writhing reaction score and serum level of PGF2α and PGF2α/PGE2 value were increased (P<0.01), the level of PGE2 was decreased (P<0.01). Compared with the model group, in the EA group and the ibuprofen group the number of writhing were decreased (P<0.05), the latency of writhing was prolonged (P<0.01), the writhing reaction scores and serum levels of PGF2α and PGF2α/PGE2 values were decreased (P<0.05, P<0.01), the levels of PGE2 were increased (P<0.01). Compared with the control group, the protein expression of NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-1β and IL-18 in the uterine tissues of rats was increased in the model group (P<0.01). Compared with the model group, the protein expression of NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-1β and IL-18 in the uterine tissues of rats was decreased in the EA group and the ibuprofen group (P<0.01, P<0.05). There was no significant difference between the EA group and the ibuprofen group in the above indexes (P>0.05).
CONCLUSION
EA could alleviate pain and uterine tissue injury in rats with PDM. The mechanism may be related to the inhibition of the activation of NLRP3 inflammasome in rat uterine tissues, thereby inhibiting pyroptosis and its inflammatory factors release.
Animals
;
Female
;
Pregnancy
;
Rats
;
Caspases
;
Dinoprost
;
Dinoprostone
;
Dysmenorrhea
;
Electroacupuncture
;
Ibuprofen
;
Inflammasomes
;
Interleukin-18
;
NLR Family, Pyrin Domain-Containing 3 Protein
;
Oxytocin
;
Phosphate-Binding Proteins
;
Pyroptosis
;
Rats, Sprague-Dawley
;
Uterus
3.Effect of total flavonoids of buckwheat flower and leaf on myocardial cell apoptosis and Wnt/β-catenin/PPARγ pathway in arrhythmic rats.
Wei-Ping HE ; Jin-Cheng LI ; Gao-Ming WANG
China Journal of Chinese Materia Medica 2023;48(1):220-225
This paper aimed to investigate the effect of total flavonoids of buckwheat flower and leaf on myocardial cell apoptosis and Wnt/β-catenin/peroxisome proliferator-activated receptor γ(PPARγ) pathway in arrhythmic rats. SD rats were randomly divided into a control group, a model group, a low-dose(20 mg·kg~(-1)) group of total flavonoids of buckwheat flower and leaf, a medium-dose(40 mg·kg~(-1)) group of total flavonoids of buckwheat flower and leaf, a high-dose(80 mg·kg~(-1)) group of total flavonoids of buckwheat flower and leaf, a propranolol hydrochloride(2 mg·kg~(-1)) group, with 12 rats in each group. Except the control group, rats in other groups were prepared as models of arrhythmia by sublingual injection of 1 mL·kg~(-1) of 0.002% aconitine. After grouping and intervention with drugs, the arrhythmia, myocardial cells apoptosis, myocardial tissue glutathione peroxidase(GSH-Px), catalase(CAT), malondialdehyde(MDA), serum interleukin-6(IL-6), prostaglandin E2(PGE2) levels, myocardial tissue apoptosis, and Wnt/β-catenin/PPARγ pathway-related protein expression of rats in each group were measured. As compared with the control group, the arrhythmia score, the number of ventricular premature beats, ventricular fibrillation duration, myocardial cell apoptosis rate, MDA levels in myocardial tissues, serum IL-6 and PGE2 levels, Bax in myocardial tissues, and Wnt1 and β-catenin protein expression levels increased significantly in the model group, whereas the GSH-Px and CAT levels, and Bcl-2 and PPARγ protein expression levels in myocardial tissues reduced significantly. As compared with the model group, the arrhythmia score, the number of ventricular premature beats, ventricular fibrillation duration, myocardial cell apoptosis rate, MDA leve in myocardial tissues, serum IL-6 and PGE2 levels, Bax in myocardial tissues, and Wnt1 and β-catenin protein expression levels reduced in the drug intervention groups, whereas the GSH-Px and CAT levels and Bcl-2 and PPARγ protein expression levels in myocardial tissues increased. The groups of total flavonoids of buckwheat flower and leaf were in a dose-dependent manner. There was no significant difference in the levels of each index in rats between the propranolol hydrochloride group and the high-dose group of total flavonoids of buckwheat flower and leaf. The total flavonoids of buckwheat flower and leaf inhibit the activation of Wnt/β-catenin pathway, up-regulate the expression of PPARγ, reduce oxidative stress and inflammatory damage in myocardial tissues of arrhythmic rats, reduce myocardial cell apoptosis, and improve the symptoms of arrhythmia in rats.
Rats
;
Animals
;
PPAR gamma/metabolism*
;
Fagopyrum/genetics*
;
Rats, Sprague-Dawley
;
bcl-2-Associated X Protein
;
beta Catenin/metabolism*
;
Interleukin-6
;
Flavonoids/pharmacology*
;
Propranolol/pharmacology*
;
Ventricular Fibrillation
;
Dinoprostone
;
Wnt Signaling Pathway
;
Plant Leaves/metabolism*
;
Flowers/metabolism*
;
Apoptosis
;
Cardiac Complexes, Premature
4.Application of different puncture techniques to inject bone cement in osteoporotic vertebral compression fractures.
China Journal of Orthopaedics and Traumatology 2023;36(1):86-91
OBJECTIVE:
To study the application of different puncture techniques to inject bone cement in osteoporotic vertebral compression fractures (OVCFs).
METHODS:
The clinical data of 282 patients with OVCFs treated from January 2017 to December 2019 were collected for a retrospective study. According to the surgical plan the patients were divided into group A and B, with 141 cases in each group. In group A, extreme lateral puncture was used to inject bone cement through unilateral puncture and bilateral puncture. In group B, bone cement was injected through unilateral pedicle puncture through pedicle approach. The operation status(operation time, radiation exposure time, bone cement injection volume, hospital stay) and complications were observed between two groups. Before operation and 6, 12 months after operation, the pain mediators such as serotonin 5-hydroxytryptamine (5-HT), prostaglandin E2(PGE2), substance P(SP) were compared, bone mineral density, anatomical parameters of the injured vertebrae (height of the anterior edge of the vertebral body, height of the posterior edge of the vertebral body, Cobb angle), visual analogue scale (VAS) and Oswestry disability index (ODI) were evaluated between two groups.
RESULTS:
There were no significant difference in operation time, radiation exposure time, hospital stay between two groups (P>0.05). The amount of bone cement injected in group A was greater than that in group B (P<0.05). The serum 5-HT, SP and PGE2 levels of group A were lower than those of group B at 12 months after operation (P<0.05). The height of anterior edge and height of the posterior edge of vertebral body in group A were greater than those of group B at 12 months after operation, Cobb angle of group A was smaller than that of group B, VAS and ODI were lower than those of group B(P<0.05). There was no significant difference in bone mineral density between two groups at 6 and 12 months postoperatively(P<0.05). There was no significant difference between two groups in postoperative complications (P>0.05).
CONCLUSION
Compared with unilateral puncture of the pedicle approach, unilateral puncture and bilateral cement injection technique is more conducive to the recovery of the injured vertebral anatomy and function, and do not prolong operation time, radiation exposure time, hospital stay, nor do increase the risk of nerve damage and bone cement leakage, and postoperative bone metabolism and bone mineral density are improved well, which is a safe and reliable surgical method for the treatment of OVCFs.
Humans
;
Spinal Fractures/surgery*
;
Fractures, Compression/surgery*
;
Bone Cements
;
Vertebroplasty/methods*
;
Retrospective Studies
;
Dinoprostone
;
Serotonin
;
Treatment Outcome
;
Osteoporotic Fractures/surgery*
;
Kyphoplasty
;
Punctures
5.Synthesis, and anti-inflammatory activities of gentiopicroside derivatives.
Qi-Li ZHANG ; Peng-Fei XIA ; Xue-Jing PENG ; Xiao-Yu WU ; Hua JIN ; Jian ZHANG ; Lei ZHAO
Chinese Journal of Natural Medicines (English Ed.) 2022;20(4):309-320
A series of 26 novel derivatives have been synthesized through structural modification of gentiopicroside, a lead COX-2 inhibitor. And their in vivo and in vitro anti-inflammatory activities have been investigated. The in vitro anti-inflammatory activities were evaluated against NO, PGE2, and IL-6 production in the mouse macrophage cell line RAW264.7 stimulated by LPS. Results showed that most compounds had good inhibitory activity. The in vivo inhibitory activities were further tested against xylene-induced mouse ear swelling. Results demonstrated that several compounds were more active than the parent compound gentiopicroside. The inhibition rate of the most active compound P23 (57.26%) was higher than positive control drug celecoxib (46.05%) at dose 0.28 mmol·kg-1. Molecular docking suggested that these compounds might bind to COX-2 and iNOS. Some of them, e.g P7, P14, P16, P21, P23, and P24, had high docking scores in accordance with their potency of the anti-inflammatory activitiy, that downregulation of the inflammatory factors, NO, PGE2, and IL-6, was possibly associated with the suppression of iNOS and COX-2. Therefore, these gentiopicroside derivatives may represent a novel class of COX-2 and iNOS inhibitors.
Animals
;
Anti-Inflammatory Agents/pharmacology*
;
Cyclooxygenase 2/chemistry*
;
Dinoprostone
;
Interleukin-6/metabolism*
;
Iridoid Glucosides
;
Mice
;
Molecular Docking Simulation
;
Pyridinolcarbamate
6.Comparison of the effectiveness and pregnancy outcomes of labor induction with dinoprostone or single-balloon catheter in term nulliparous women with borderline oligohydramnios.
Yongqing ZHANG ; Luping CHEN ; Guohui YAN ; Menglin ZHOU ; Zhengyun CHEN ; Zhaoxia LIANG ; Danqing CHEN
Chinese Medical Journal 2022;135(6):681-690
BACKGROUNDS:
At present, there is no consensus on the induction methods in term pregnancy with borderline oligohydramnios. This study aimed to compare the effectiveness and pregnancy outcomes of labor induction with dinoprostone or single-balloon catheter (SBC) in term nulliparous women with borderline oligohydramnios.
METHODS:
We conducted a retrospective cohort study from January 2016 to November 2018. During the study period, a total of 244 cases were enrolled. Of these, 103 cases were selected for induction using dinoprostone and 141 cases were selected for induction with SBC. The pregnancy outcomes between the two groups were compared. Primary outcomes were successful vaginal delivery rates. Secondary outcomes were maternal and neonatal adverse events. Multivariate logistic regression was used to assess the risk factors for vaginal delivery failure in the two groups.
RESULTS:
The successful vaginal delivery rates were similar between the dinoprostone group and the SBC group (64.1% [66/103] vs. 59.6%, [84/141] P = 0.475), even after adjustment for potential confounding factors (adjusted odds ratio [aOR]: 1.07, 95% confidence interval [CI]: 0.57-2.00, P = 0.835). The incidence of intra-amniotic infection was lower in the dinoprostone group than in the SBC group (1.9% [2/103] vs. 7.8%, [11/141] P < 0.001), but the presence of non-reassuring fetal heart rate was higher in the dinoprostone group than in the SBC group (12.6% [13/103] vs. 0.7%, [1/141] P < 0.001). Multivariate logistic regression showed that nuchal cord was a risk factor for vaginal delivery failure after induction with dinoprostone (aOR: 6.71, 95% CI: 1.96-22.95). There were three factors related to vaginal delivery failure after induction with SBC, namely gestational age (aOR: 1.51, 95% CI: 1.07-2.14), body mass index (BMI) >30 kg/m2 (aOR: 2.98, 95% CI: 1.10-8.02), and fetal weight >3500 g (aOR: 2.49, 95% CI: 1.12-5.50).
CONCLUSIONS
Term nulliparous women with borderline oligohydramnios have similar successful vaginal delivery rates after induction with dinoprostone or SBC, with their advantages and disadvantages. In women with nuchal cord, the risk of vaginal delivery failure is increased if dinoprostone is used in the induction of labor. BMI >30 kg/m2, large gestational age, and estimated fetal weight >3500 g are risk factors for vaginal delivery failure after induction with SBC.
Administration, Intravaginal
;
Catheters
;
Dinoprostone/therapeutic use*
;
Female
;
Fetal Weight
;
Humans
;
Infant, Newborn
;
Labor, Induced/methods*
;
Nuchal Cord
;
Oligohydramnios
;
Oxytocics
;
Pregnancy
;
Pregnancy Outcome
;
Retrospective Studies
7.The use of dinoprostone versus evening primrose oil for cervical ripening in women who will undergo hysteroscopy: A randomized controlled trial
Jirah Joy De Guzman ; Maria Luisa C. Tanchoco
Philippine Journal of Reproductive Endocrinology and Infertility 2022;19(2):41-50
Objective:
To compare the efficacy of Dinoprostone gel versus intravaginal evening primrose
oil capsule as cervical ripening agents for operative hysteroscopy…. and to compare the length
of time to achieve a 10mm cervical dilatation prior to operative hysteroscopy.
Methods:
This is a two-arm randomized controlled trial done in a tertiary training institution.
Group A and B received Dinoprostone gel and EPO for cervical ripening, respectively. Population
consisted of women admitted for operative hysteroscopy, aged between 19-56 years old, and
with closed cervix.
Results:
Thirty-eight (38) patients mostly pre-menopausal with mean age of 41, without history
of uterine surgery, and presented with abnormal uterine bleeding, were included. Significant
difference was observed in initial cervical dilatation between Dinoprostone gel(5.63 mm) versus
EPO(4.21mm). Most patients in EPO group were pain-free while Dinoprostone group experienced
tolerable pain. Use of Dinoprostone was 4x more expensive versus EPO.
Conclusion
Both agents were effective in dilating the cervix prior to operative hysteroscopy.
Nevertheless, EPO may be superior and acceptable due to reduced cost, patient convenience
and acceptability, and ease of administration.
Dinoprostone
8.Mechanism of Shaofu Zhuyu Decoction in treatment of endometriosis-associated dysmenorrhea with syndrome of cold coagulation and blood stasis based on MSK1/2.
Yuan-Huan CHEN ; Hai-Yan MAO ; Quan-Sheng WU ; Xiao-Hua ZHANG ; Jian SHEN ; Peng FENG ; Can-Can HUANG ; Xiu-Jia JI
China Journal of Chinese Materia Medica 2022;47(17):4674-4681
This study aims to decipher the mechanism underlying the effect of Shaofu Zhuyu Decoction on endometriosis(EMT)-associated dysmenorrhea in rats with the syndrome of cold coagulation and blood stasis based on mitogen-and stress-activated protein kinase 1/2(MSK1/2).We employed a random number table to randomly assign SPF female non-pregnant rats into the sham group, and treated the rest rats with autologous transplantation+refrigerator freezing for the modeling of the syndrome of cold coagulation and blood stasis.The modeled rats were then randomly assigned into the control group and high-, medium-and low-dose Shaofu Zhuyu Decoction groups.The rats in the low-, medium-, and high-dose decoction groups were respectively administrated with 9, 4.5, and 2.3 g·kg~(-1) decoction through gavage once a day for 2 consecutive weeks, and those in the control group were administrated with 0.24 mg·kg~(-1) gestrinone through gavage once every 3 days for 2 weeks.After that, the size of ectopic focus in each rat was measured via laparotomy.Enzyme-linked immunosorbent assay(ELISA) was adopted to determine the expression of interleukin(IL)-6, IL-10, prostaglandin E2(PGE2), tumor necrosis factor-α(TNF-α).Western blot was employed to determine the protein levels of MSK1/2 and dual-specificity phosphatase 1(DUSP1) and real-time quantitative polymerase chain reaction(RT-PCR) to determine the mRNA levels of the two genes in rat eutopic endometrial tissue.Compared with the sham group, the model group showed increased levels of IL-6, PGE2, and TNF-α while decrease level of IL-10 in the serum(P<0.01).Compared with the model group, the high-and medium-dose decoction groups and the gestrinone group had declined levels of IL-6, PGE2, and TNF-α while risen level of IL-10 in the serum(P<0.01).The model group had lower protein levels and mRNA levels of MSK1/2 and DUSP1 in the eutopic endometrial tissue than the sham group(P<0.01). The high-and medium-dose decoction groups and the gestrinone group had higher protein and mRNA levels of MSK1/2 and DUSP1 in the eutopic endometrial tissue than the model group(P<0.01).The results indicated that Shaofu Zhuyu Decoction can regulate the abnormal expression of pro-inflammatory cytokines TNF-α, IL-6, and PGE2 and anti-inflammatory cytokines IL-10 and DUSP1 via MSK1/2 to alleviate EMT-associated dysmenorrhea in rats with the syndrome of cold coagulation and blood stasis.
Animals
;
Female
;
Rats
;
Anti-Inflammatory Agents/therapeutic use*
;
Cytokines
;
Dinoprostone
;
Drugs, Chinese Herbal/therapeutic use*
;
Dual-Specificity Phosphatases
;
Dysmenorrhea/genetics*
;
Endometriosis/genetics*
;
Gestrinone/therapeutic use*
;
Interleukin-10
;
Interleukin-6
;
Mitogen-Activated Protein Kinase 8/therapeutic use*
;
Mitogens/therapeutic use*
;
RNA, Messenger
;
Tumor Necrosis Factor-alpha/metabolism*
9.Potential pharmacodynamic substances of Laportea bulbifera in treatment of rheumatoid arthritis based on serum pharmacochemistry and pharmacology.
Juan TANG ; Qing ZHANG ; Dan WU ; Si-Ying CHEN ; Yi CHEN ; Yue-Ting LI ; Lin ZHENG ; Yong HUANG ; Yan-Yu LAN ; Yong-Lin WANG ; Zi-Peng GONG
China Journal of Chinese Materia Medica 2022;47(17):4755-4764
The present study investigated the pharmacodynamic material basis of Laportea bulbifera in the treatment of rheumatoid arthritis. Firstly, human rheumatoid arthritis fibroblast-like synoviocyte line MH7A was cultured in vitro and treated with tumor necrosis factor alpha(TNF-α, 50 ng·mL~(-1)). The proliferation and the levels of inflammatory cytokines such as prostaglandin E2(PGE2), interleukin-1β(IL-1β), and interleukin-6(IL-6) of the MH7A cells exposed to the serum containing L. bulbifera were determined to evaluate the anti-rheumatoid arthritis effects of the serum. Furthermore, the ultra-performance liquid chromatography tandem mass spectrometry fingerprints of the L. bulbifera crude extract, the drug-containing serum, and the drug-free serum were compared to identify the compounds newly generated in the serum after oral administration of the extract. According to the peak areas of common peaks and the results of anti-rheumatoid arthritis effect test, the active components were identified. The serum containing L. bulbifera significantly inhibited the proliferation of the MH7A cells activated by TNF-α and the expression of PGE2, IL-6, and IL-1β. Thirty newly generated compounds were detected in the drug-containing serum. Among them, neochlorogenic acid, cryptochlorogenic acid, chlorogenic acid, rutin, isoquercitrin, luteoloside, kaempferol-3-O-rutinoside, and quercitrin were also present in the crude extract. Twelve characteristic peaks(3, 7, 8, 14, 18, 19, 21, 23, 24, m6, m7, and m15) were significantly correlated with the pharmaceutical effect. According to the correlations, neochlorogenic acid, cryptochlorogenic acid, and chlorogenic acid had great contributions to the anti-rheumatoid arthritis activity. This study preliminarily clarified the potential pharmacodynamic substances of L. bulbifera in the treatment of rheumatoid arthritis, which laid a theoretical and experimental foundation for further development and application of the medicinal plant.
Animals
;
Arthritis, Experimental/drug therapy*
;
Arthritis, Rheumatoid/drug therapy*
;
Chlorogenic Acid/analogs & derivatives*
;
Cytokines/metabolism*
;
Dinoprostone
;
Humans
;
Interleukin-1beta/genetics*
;
Interleukin-6
;
Plant Extracts/therapeutic use*
;
Quinic Acid/analogs & derivatives*
;
Rutin
;
Tumor Necrosis Factor-alpha/metabolism*
;
Urticaceae/chemistry*
10.Effect of Maxing Shigan Decoction and dissembled prescriptions against airway inflammation in RSV-aggravated asthma and mechanism of regulating TRPV1.
Meng-Wen LI ; Xin-Sheng FAN ; Li-Ping ZHOU ; Mo LIU ; Er-Xin SHANG
China Journal of Chinese Materia Medica 2022;47(21):5872-5881
This study investigated the effect of Maxing Shigan Decoction(MXSGD) and its disassembled prescriptions against the airway inflammation in respiratory syncytial virus(RSV)-aggravated asthma and the regulation of transient receptor potential vanilloid-1(TRPV1). To be specific, ovalbumin(OVA) and RSV were used to induce aggravated asthma in mice(female, C57BL/6). Then the model mice were intervened by MXSGD and the disassembled prescriptions. The eosinophil(EOS) in peripheral blood, inflammatory cells in bronchoalveolar lavage fluid(BALF), enhanced pause(Penh) variation, and lung pathological damage in each group were observed, and the changes of interleukin(IL)-4, IL-13, substance P(SP), and prostaglandin E2(PGE2) in BALF were mea-sured by enzyme-linked immunosorbent assay(ELISA). Quantitative real time polymerase chain reaction(qPCR) and Western blot were used to detect mRNA and protein of TRPV1 in mouse lung tissue. In the in vitro experiment, 16 HBE cells were stimulated with IL-4 and RSV. Then the changes of TRPV1 expression after the intervention with the serum containing MXSGD and its disassembled prescriptions were observed. Besides, the intracellular Ca~(2+) level after the stimulation with TRPV1 agonist was evaluated. The results showed that the mice in the model group had obvious asthma phenotype, the levels of various inflammatory cells in the peripheral blood and BALF and Penh were significantly increased(P<0.05, P<0.01), and the lung tissue was severely damaged compared with the control group. Compared with the model group, the levels of EOS in the peripheral blood and BALF were significantly decreased in the MXSGD group, the SG group and the MXC group(P<0.05, P<0.01). The levels of WBC and neutrophils in BALF were significantly decreased in the MXSGD group and SG group(P<0.01), the levels of neutrophils in BALF were decreased in the MXC group(P<0.05). The improvement effect of the MXGSD on the level of inflammatory cells in peripheral blood and BALF was better than that of two disassembled groups(P<0.05, P<0.01). After 50 mg·mL~(-1) acetylcholine chloride stimulation, the Penh values of the MXSGD group and the MXC group significantly decreased(P<0.01), and the Penh value of the SG group decreased(P<0.05). The levels of IL-4, IL-13, PGE2 and SP in BALF could be significantly decreased in the MXSGD group(P<0.05, P<0.01), the levels of IL-13 and PGE2 in BALF could be decreased in the MXC group(P<0.05, P<0.01), and the levels of IL-13, PGE2 and SP in BALF could be decreased in the SG group(P<0.05, P<0.01). MXSGD could down-regulate the protein and mRNA expression of TRPV1 in lung tissue(P<0.05, P<0.01). The serum containing MXSGD and its disassembled prescriptions could down-regulate TRPV1 expression in 16 HBE cells stimulated by IL-4 combined with RSV and inhibit the inward flow of Ca~(2+) induced by TRPV1 agonist, especially the serum containing MXSGD which showed better effect than the serum containing disassembled ones(P<0.05). In vivo and in vitro experiments verified the protective effect of MXSGD and its disassembled prescriptions against airway inflammation in RSV-exacerbated asthma, the whole decoction thus possessed synergy in treating asthma, with better performance than the dissembled prescriptions. Different groups of prescription had made contributions in improving airway hyperresponsiveness, anti-allergy and anti-inflammation. The mechanism is the likelihood that it regulates TRPV1 channel and levels of related inflammatory mediators.
Female
;
Mice
;
Animals
;
Interleukin-13/metabolism*
;
Interleukin-4/metabolism*
;
Dinoprostone
;
Mice, Inbred BALB C
;
Mice, Inbred C57BL
;
Asthma/chemically induced*
;
Lung
;
Bronchoalveolar Lavage Fluid
;
Ovalbumin/adverse effects*
;
Inflammation/metabolism*
;
RNA, Messenger/metabolism*
;
Prescriptions
;
Disease Models, Animal
;
TRPV Cation Channels/metabolism*


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