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Discovery of Fungus-Derived Nornidulin as a Novel TMEM16A Inhibitor: A Potential Therapy to Inhibit Mucus Secretion in Asthma 真菌衍生去甲脲作为一种新的TMEM16A抑制剂的发现:抑制哮喘粘液分泌的潜在疗法
Q2 Medicine Pub Date : 2023-11-01 DOI: 10.2147/jep.s427594
Pawin Pongkorpsakol, Chantapol Yimnual, Wilasinee Satianrapapong, Nichakorn Worakajit, Suchada Kaewin, Praphatsorn Saetang, Vatcharin Rukachaisirikul, Chatchai Muanprasat
Introduction Inhibition of Ca2+-activated transmembrane protein 16A (TMEM16A) Cl− channels has been proposed to alleviate mucus secretion in asthma. In this study, we identified a novel class of TMEM16A inhibitors from natural sources in airway epithelial Calu-3 cells and determine anti-asthmatic efficacy of the most potent candidate in a mouse model of asthma. Methods For electrophysiological analyses, IL-4-primed Calu-3 cell monolayers were mounted in Ussing chamber and treated with various fungus-derived depsidones prior to the addition of UTP, ionomycin, thapsigargin, or Eact to stimulate TMEM16A Cl− current. Ca2+-induced mucus secretion in Calu-3 cell monolayers was assessed by determining MUC5AC protein remaining in the cells using immunofluorescence staining. OVA-induced female BALB/c mice was used as an animal model of asthma. After the course of induction, cellular and mucus components in bronchoalveolar lavage were analyzed. Lungs were fixed and undergone with H&E and PAS staining for the evaluation of airway inflammation and mucus production, respectively. Results The screening of fungus-derived depsidones revealed that nornidulin completely abolished the UTP-activated TMEM16A current in Calu-3 cell monolayers with the IC50 and a maximal effect being at ~0.8 µM and 10 µM, respectively. Neither cell viability nor barrier function was affected by nornidulin. Mechanistically, nornidulin (10 µM) suppressed Cl− currents induced by ionomycin (a Ca2+-specific ionophore), thapsigargin (an inhibitor of the endoplasmic reticulum Ca2+ ATPase), and Eact (a putative TMEM16A activator) without interfering with intracellular Ca2+ ([Ca2+]i) levels. These results suggest that nornidulin exerts its effect without changing [Ca2+]i, possibly through direct effect on TMEM16A. Interestingly, nornidulin (at 10 µM) reduced Ca2+-dependent mucus release in the Calu-3 cell monolayers. In addition, nornidulin (20 mg/kg) inhibited bronchoalveolar mucus secretion without impeding airway inflammation in ovalbumin-induced asthmatic mice. Discussion and Conclusion Our study revealed that nornidulin is a novel TMEM16A inhibitor that suppresses mucus secretion without compromising immunologic activity. Further development of nornidulin may provide a new remedy for asthma or other diseases associated with allergic mucus hypersecretion without causing opportunistic infections.
已经提出通过抑制ca2 +激活的跨膜蛋白16A (TMEM16A) Cl -通道来缓解哮喘患者的粘液分泌。在这项研究中,我们从气道上皮Calu-3细胞的天然来源中发现了一类新的TMEM16A抑制剂,并在哮喘小鼠模型中确定了最有效的候选抗哮喘功效。方法:为了进行电生理分析,将il -4引物的Calu-3细胞单层置于Ussing chamber中,在加入UTP、离子霉素、thapsigargin或E act之前,用各种真菌衍生的depsidones处理,以刺激TMEM16A Cl−电流。采用免疫荧光染色法测定细胞内MUC5AC蛋白,评价ca2 +诱导的Calu-3细胞单层粘液分泌。采用ova诱导的雌性BALB/c小鼠作为哮喘动物模型。诱导过程结束后,对支气管肺泡灌洗液中的细胞成分和黏液成分进行分析。固定肺,分别进行H&E和PAS染色,评估气道炎症和粘液产生情况。结果:真菌来源的去髓苷类化合物的筛选表明,去髓苷完全消除了Calu-3细胞单层中utp激活的TMEM16A电流,ic50,最大作用分别在~0.8 μM和10 μM。细胞活力和屏障功能均未受去髓蛋白的影响。从机制上看,nornidulin (10 μM)抑制了离子霉素(一种ca2 +特异性离子载体)、thapsigargin(一种内质网ca2 + atp酶抑制剂)和E act(一种推测的TMEM16A激活剂)诱导的Cl -电流,而不干扰细胞内ca2 + ([ca2 +] i)水平。这些结果表明,去髓蛋白的作用不改变[ca2 +] i,可能是通过直接作用于TMEM16A来实现的。有趣的是,去nidulin (10 μM)减少Calu-3细胞单层中ca2 +依赖性粘液的释放。此外,去甲肼(20mg /kg)可抑制卵清蛋白诱导的哮喘小鼠支气管肺泡粘液分泌,但不妨碍气道炎症。讨论与结论:我们的研究表明去甲髓苷是一种新型的TMEM16A抑制剂,可以抑制粘液分泌而不影响免疫活性。去甲脲的进一步发展可能为哮喘或其他与过敏性粘液分泌过多相关的疾病提供新的治疗方法,而不会引起机会性感染。关键词:TMEM16a,去nidulin,哮喘,粘液分泌,气道上皮
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引用次数: 0
Evaluation of Anti-Inflammatory Activity of the Methanol Extracts of Premna schimperi Engl (Lamiaceae) Leaves in Rats 水芹叶甲醇提取物对大鼠抗炎活性的评价
Q2 Medicine Pub Date : 2023-11-01 DOI: 10.2147/jep.s432615
Melese Arega, Aschalew Nardos, Asfaw Debella, Beyene Dereje, Lidet Terefe, Abiy Abebe
Background: Even though it is a protective reaction, inflammation continues to be one of the most challenging medical disorders. The current conventional anti-inflammatory drugs have many undesirable health effects and are in need of newer drugs. The purpose of this study was to evaluate the anti-inflammatory effects of an aqueous methanol crude extract of Premna schimperi leaves. Methods: Premna schimperi leaf was extracted with 80% methanol and concentrated; the concentrated extract was used to evaluate the acute toxicity and anti-inflammatory effects. For the acute toxicity study, a single dose of Premna schimperi extract at a dose of 2000 mg/kg was administered and observed for 14 days. Acute, sub-acute, and chronic anti-inflammatory models were employed to evaluate the anti-inflammatory effect of the extract compared to the standard drug. Data were analyzed with SPSS V. 27, and the significance was established with a one-way ANOVA followed by a post hoc Tukey’s test. Results: Acute oral toxicity testing at a dose of 2000 mg/kg did not show any sign of toxicity. According to the phytochemical study, the plants contained flavonoids, terpenoids, tannins, cardiac glycosides, steroids, phenolics, and anthraquinones. The extract doses of 200 mg/kg, 400 mg/kg, and 800 mg/kg of extracts effectively (p< 0.001) reduced paw edema in the acute and sub-acute models of inflammation. When compared to the negative control group, all tested doses in the chronic model significantly (p< 0.05) decreased the production of exudates and the amount of granuloma tissue. Conclusion: Premna schimperi displayed significant anti-inflammatory activity. The tested doses inhibit the formation of edema, granulomas, and exudates. Keywords: anti-inflammation, carrageenan, indomethacin, paw edema, Premna schimperi
背景:尽管炎症是一种保护性反应,但它仍然是最具挑战性的医学疾病之一。目前传统的抗炎药物对健康有许多不良影响,需要新的药物。本研究的目的是评价水溶甲醇粗提物的抗炎作用。方法:用80%甲醇提取香盆草叶,浓缩;用浓缩提取物评价其急性毒性和抗炎作用。急性毒性研究采用单次给药,剂量为2000 mg/kg,观察14天。采用急性、亚急性和慢性抗炎模型,与标准药物比较,评价提取物的抗炎作用。数据用SPSS V. 27进行分析,通过单因素方差分析和事后Tukey检验确定显著性。结果:急性口服毒性试验,剂量为2000mg /kg,未见任何毒性迹象。根据植物化学研究,这些植物含有黄酮类、萜类、单宁、心苷类、类固醇、酚类和蒽醌类。200 mg/kg、400 mg/kg和800 mg/kg提取物均能有效减轻急性和亚急性炎症模型大鼠足部水肿(p< 0.001)。与阴性对照组比较,慢性模型各剂量均显著(p< 0.05)降低了渗出液的产生和肉芽肿组织的数量。结论:水芹具有明显的抗炎活性。试验剂量抑制水肿、肉芽肿和渗出物的形成。关键词:抗炎,卡拉胶,吲哚美辛,足跖水肿,凤尾草
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引用次数: 0
Evaluation of Anti-Diarrheal Activities of the 80% Methanol Extract and Solvent Fractions of Maesa lanceolata Forssk (Myrsinaceae) Leaves in Mice. 山杨叶80%甲醇提取物和溶剂组分对小鼠抗腹泻活性的评价。
Q2 Medicine Pub Date : 2023-10-25 eCollection Date: 2023-01-01 DOI: 10.2147/JEP.S429403
Alemayehu Megersa, Beyene Dereje, Meaza Adugna, Kefyalew Ayalew Getahun, Eshetie Melese Birru

Background: Due to the limits of present antidiarrheal medications, it is critical to seek novel, safe, and inexpensive antidiarrheal agents. Thus, the goal of this study was to assess the antidiarrheal activity of 80% methanol crude extract and solvent fractions of Maesa lanceolata leaves in mice.

Methods: Leaf powder was extracted by 80% methanol and then fractionated with n-hexane, ethyl acetate, and distilled water. At 100, 200, and 400 mg/kg, the effects of the crude extract on castor oil-induced diarrhea, enteropooling, and gastrointestinal motility tests were investigated. Tween 2% and atropine used as negative and positive controls, respectively. A gastrointestinal motility test was used to explore the anti-motility effects. Data were analyzed with SPSS V. 26, and the significance was established with a one-way ANOVA followed by a post hoc Tukey's test.

Results: The crude extract delayed the onset of diarrhea and significantly reduced the number of fecal drops at 100 (p<0.05), 200 and 400 mg/kg (p<0.001). Similarly, the number and weight of wet feces, as well as total fresh feces, were reduced at 200 (p<0.05) and 400 mg/kg (p<0.001) compared to Tween 2%. The enteropooling test demonstrated that the extracts significantly reduced the volume and weight of intestine content at 200 (p<0.05) and 400 mg/kg (p<0.001). The anti-motility activity test revealed that the all extracts decreased gastrointestinal motility significantly (p<0.001). The ethyl acetate fraction significantly reduced gastrointestinal transit time at all doses (p<0.001). At 400 mg/kg, the activities of the n-hexane fraction were significant (p<0.01). The efficacy of the residual aqueous fraction on gastrointestinal motility was significant at 200 (p<0.05) and 400 mg/kg (p<0.001).

Conclusion: The 80% methanol extract of Maesa lanceolata Forssk leaf and solvent fractions were shown to exhibit potent antidiarrheal activity in the current study.

背景:由于目前止泻药的局限性,寻找新型、安全、廉价的止泻药至关重要。因此,本研究的目的是评估香叶80%甲醇粗提取物和溶剂组分对小鼠的止泻活性。方法:用80%甲醇提取叶末,用正己烷、乙酸乙酯和蒸馏水进行分级。在100、200和400 mg/kg下,研究了粗提取物对蓖麻油诱导的腹泻、肠汇集和胃肠动力测试的影响。2%吐温和阿托品分别作为阴性对照和阳性对照。采用胃肠动力试验来探讨其抗运动作用。数据用SPSS V.26进行分析,并通过单因素方差分析和事后Tukey检验确定显著性。结果:该粗提取物延缓了腹泻的发作,并在100时显著减少了粪便滴下的次数(P结论:在本研究中,毛叶80%甲醇提取物和溶剂组分显示出强大的止泻活性。
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引用次数: 1
Anti-Diabetic Effects of the 80% Methanolic Extract of Datura Stramonium Linn (Solanaceae) Leaves in Streptozotocin- Induced Diabetic Mice. 曼陀罗叶80%甲醇提取物对链脲佐菌素诱导的糖尿病小鼠的抗糖尿病作用。
Q2 Medicine Pub Date : 2023-10-18 eCollection Date: 2023-01-01 DOI: 10.2147/JEP.S426925
Temesgen Baylie, Assefa Kebad, Tiget Ayelgn, Markeshaw Tiruneh, Kibur Hunie Tesfa

Background: Managing diabetes mellitus with currently available drugs is costly, and the chances of side effects are high, leading to further studies for new and better medications from plant sources with the affordable and lower side effects. This study aimed to evaluate the anti-diabetic effects of Datura stramonium Linn (Solanaceae) Leaves Extract in Streptozotocin- Induced Diabetic Mice.

Methods: Male Swiss albino mice were induced into diabetes using 150mg/kg of STZ. Mice were allocated randomly into six groups, five mice per group. Group I was a normal control, Group II was Diabetic negative control, group III was Diabetic positive control, Group IV-VI were Diabetic Mice that treated with extract (100, 200 and 400 mg/kg) for 14 days. The FBG measurements were done on 0, 7th, and 14th days of treatment. After 14th day of treatment the mice were anesthetized with diethyl ether. Then, blood was drawn by cardiac puncture to assess TC, TG, LDL-C, and HDL-C. The antioxidant activity of the extract was determined using a DPPH assay. The data were entered into Epi-Data version 4.6, exported to SPSS version 26.0, and analyzed using a one-way ANOVA followed by a Tukey post hoc test. P < 0.05 was considered statistically significant.

Results: The extract of D. stramonium reduced the FBG level by 19.71%, 30.27%, 40.95%, and 45.67%, respectively, for D. stramonium 100, 200, 400, and GLC 5 mg/kg on the 14th day of treatment. Diabetic mice treated with D. stramonium for 14 days   showed a significant decrease in serum TC, LDL, and serum TG and a significant increase in body weight, and HDL level as compared to diabetic negative control. Antioxidant activities of the leaves extract were comparable to ascorbic acid with an IC50 of 172.79 μg/mL.

Conclusion: These findings revealed that the D. stramonium leaves extract possesses significant Anti-diabetic activities.

背景:用目前可用的药物治疗糖尿病成本高昂,副作用发生的几率很高,因此需要进一步研究从植物来源获得的新的更好的药物,这些药物具有负担得起和更低的副作用。本研究旨在评价曼陀罗叶提取物对链脲佐菌素诱导的糖尿病小鼠的抗糖尿病作用。将小鼠随机分为六组,每组五只。第一组为正常对照,第二组为糖尿病阴性对照,第三组为糖尿病阳性对照,第IV-VI组为用提取物(100、200和400 mg/kg)治疗14天的糖尿病小鼠。FBG测量在治疗的第0天、第7天和第14天进行。治疗14天后,用乙醚麻醉小鼠。然后,通过心脏穿刺抽血以评估TC、TG、LDL-C和HDL-C。使用DPPH测定法测定提取物的抗氧化活性。将数据输入Epi data 4.6版,导出到SPSS 26.0版,并使用单因素方差分析和Tukey事后检验进行分析。P<0.05被认为具有统计学意义。结果:在治疗第14天,对于100、200、400和GLC 5mg/kg的草,草提取物分别降低了19.71%、30.27%、40.95%和45.67%的FBG水平。stramonium治疗糖尿病小鼠14天  与糖尿病阴性对照组相比,血清TC、LDL和血清TG显著降低,体重和HDL水平显著增加。其抗氧化活性与抗坏血酸相当,IC50为172.79μg/mL。
{"title":"Anti-Diabetic Effects of the 80% Methanolic Extract of Datura Stramonium Linn (Solanaceae) Leaves in Streptozotocin- Induced Diabetic Mice.","authors":"Temesgen Baylie,&nbsp;Assefa Kebad,&nbsp;Tiget Ayelgn,&nbsp;Markeshaw Tiruneh,&nbsp;Kibur Hunie Tesfa","doi":"10.2147/JEP.S426925","DOIUrl":"10.2147/JEP.S426925","url":null,"abstract":"<p><strong>Background: </strong>Managing diabetes mellitus with currently available drugs is costly, and the chances of side effects are high, leading to further studies for new and better medications from plant sources with the affordable and lower side effects. This study aimed to evaluate the anti-diabetic effects of <i>Datura stramonium</i> Linn (Solanaceae) Leaves Extract in Streptozotocin- Induced Diabetic Mice.</p><p><strong>Methods: </strong>Male Swiss albino mice were induced into diabetes using 150mg/kg of STZ. Mice were allocated randomly into six groups, five mice per group. Group I was a normal control, Group II was Diabetic negative control, group III was Diabetic positive control, Group IV-VI were Diabetic Mice that treated with extract (100, 200 and 400 mg/kg) for 14 days. The FBG measurements were done on 0, 7th, and 14th days of treatment. After 14th day of treatment the mice were anesthetized with diethyl ether. Then, blood was drawn by cardiac puncture to assess TC, TG, LDL-C, and HDL-C. The antioxidant activity of the extract was determined using a DPPH assay. The data were entered into Epi-Data version 4.6, exported to SPSS version 26.0, and analyzed using a one-way ANOVA followed by a Tukey post hoc test. P < 0.05 was considered statistically significant.</p><p><strong>Results: </strong>The extract of <i>D. stramonium</i> reduced the FBG level by 19.71%, 30.27%, 40.95%, and 45.67%, respectively, for <i>D. stramonium</i> 100, 200, 400, and GLC 5 mg/kg on the 14th day of treatment. Diabetic mice treated with <i>D. stramonium</i> for 14 days   showed a significant decrease in serum TC, LDL, and serum TG and a significant increase in body weight, and HDL level as compared to diabetic negative control. Antioxidant activities of the leaves extract were comparable to ascorbic acid with an IC50 of 172.79 μg/mL.</p><p><strong>Conclusion: </strong>These findings revealed that the <i>D. stramonium</i> leaves extract possesses significant Anti-diabetic activities.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"15 ","pages":"375-389"},"PeriodicalIF":0.0,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a7/3e/jep-15-375.PMC10590592.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49690832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Efficacy of Topical Formulation Containing Ciplukan (Physalis angulata Linn.) in Modulating Interleukin-17 and Interferon Gamma Expression in Mice (Mus musculus) Psoriasis Model. 含有Ciplukan(Physalis angulata Linn.)的局部制剂在小鼠(Mus musculus)银屑病模型中调节白细胞介素-17和干扰素γ表达的功效。
Q2 Medicine Pub Date : 2023-10-09 eCollection Date: 2023-01-01 DOI: 10.2147/JEP.S427615
Oki Suwarsa, Hartati Purbo Dharmadji, Enny Rohmawaty, Shela Mareta, Hendra Gunawan, Reiva Farah Dwiyana, Pati Aji Achdiat, Endang Sutedja, Miranti Pangastuti

Background: Interleukin 17 (IL-17) and interferon gamma (IFN-γ) play a role in the pathogenesis of psoriasis vulgaris (PV). Topical corticosteroids are still utilised as first-line therapy for mild to moderate PV. However, long-term use of corticosteroid is associated with various side effects. Physalis angulata Linn. (Ciplukan) possesses anti-inflammatory properties that could serve as a potential alternative topical therapy for PV.

Objective: To assess the efficacy of topical ciplukan as an anti-inflammatory agent targeting the expression of IL-17 and IFN-γ.

Methods: Psoriasis was induced using imiquimod cream, therefore divided into five groups. Group I, the psoriasis control group, received only imiquimod cream. Groups C1 and C2 received imiquimod cream followed by a mixture of Ciplukan and vaseline in a 1:2 and 1:4 ratio, respectively. Group M, the standard therapy group, received imiquimod cream, followed by mometasone furoate cream. Lastly, group V, the vehicle group, received imiquimod cream followed by vaseline album. Expression of IL-17 and IFN-γ in mice's skin tissue was analysed using reverse transcription polymerase chain reaction (RT-PCR) after seven days of treatment.

Results: The mean expression of IL-17 in Group C1 (22.60) was significantly lower (p = 0.012) than in the psoriasis control group (23.60), and there was no significant difference (p = 0.613) in Group M (22.41). The mean expression of IFN-γ in Group C1 (26.97) and Group C2 (27.03) was also significantly lower (p = 0.026 and p = 0.026, respectively) than Group I (28.80), and there was no significant difference (p = 0.180 and p = 0.093, respectively) than Group M (26.03).

Conclusion: Expression of IL-17 and IFN-γ in the ciplukan group is lower than in the psoriasis control group, and there is no significant difference compared to the standard therapy group.

背景:白细胞介素17(IL-17)和干扰素-γ(IFN-γ)在寻常型银屑病(PV)的发病机制中发挥作用。局部皮质类固醇仍然被用作轻度至中度PV的一线治疗。然而,长期使用皮质类固醇会产生各种副作用。棱藻。(Ciplukan)具有抗炎特性,可作为PV的潜在替代局部治疗方法。目的:评估局部Ciplukan作为靶向IL-17和IFN-γ表达的抗炎剂的疗效。方法:用咪喹莫特乳膏诱导银屑病,分为五组。第一组,银屑病对照组,仅接受咪喹莫特乳膏。C1组和C2组接受咪喹莫特乳膏,然后分别以1:2和1:4的比例接受西普卢康和凡士林的混合物。M组为标准治疗组,给予咪喹莫特乳膏,随后给予糠酸莫米松乳膏。最后,第五组,即赋形剂组,接受咪喹莫特乳膏,然后接受凡士林相册。治疗7天后,使用逆转录聚合酶链式反应(RT-PCR)分析小鼠皮肤组织中IL-17和IFN-γ的表达。结果:C1组(22.60)的IL-17平均表达显著低于银屑病对照组(23.60)(p=0.012),M组(22.41)无显著差异(p=0.0613)。C1组(26.97)和C2组(27.03)的IFN-γ平均表达也显著低于I组(28.80)(分别为p=0.026和p=0.026),结论:白细胞介素17和干扰素-γ在ciplukan组的表达低于银屑病对照组,与标准治疗组相比无显著差异。
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引用次数: 0
Chemopreventive Activity of 80% Methanol Leaf Extract of Vernonia auriculifera Hiern (Asteraceae) Against Dimethylhydrazine-Induced Colorectal Carcinogenesis in Rats. Vernonia auriculifera Hiern(菊科)80%甲醇叶提取物对二甲基肼诱导的大鼠结直肠癌发生的化学预防活性
Q2 Medicine Pub Date : 2023-09-04 eCollection Date: 2023-01-01 DOI: 10.2147/JEP.S421338
Yohannes Tsegyie Wondmkun, Ephrem Engidawork, Wajana Lako Labisso, Anteneh Belete, Solomon Tesfaye, Yonas Girma Shumiye

Background: Vernonia auriculifera Hiern (Asteraceae) is among Ethiopian herbal medicines that are traditionally used to treat skin and gastrointestinal cancers. In this study, the chemopreventive potential of Vernonia auriculifera leaf extract in dimethylhydrazine (DMH)-induced colorectal carcinogenesis in rats was investigated.

Methods: Rats were assigned to nine groups (normal, positive, and negative control groups, and three pre- and three post-initiation groups). Except for the normal control group (administered with 1 mL/100 g distilled water), the remaining eight groups were given DMH (20 mg/kg) intraperitoneally (ip) for 15 consecutive weeks to induce colorectal tumours. The extract was given orally to the pre-initiation and post-initiation groups at doses of 100, 200, and 400 mg/kg before and after the induction of cancer, respectively. The positive control group was treated with aspirin (60 mg/kg/day) orally for the whole experimental period. Parameters including body weight, average tumour number, size, progression, incidence, total cholesterol, serum total protein, and triglyceride levels were determined. The cytotoxic activity of the extract in Caco-2 cells was evaluated using the MTT assay, and the antioxidant activity of the extract was also assessed using 2.2-diphenyl-1-picrylhydrazine (DPPH) and reducing power methods. Moreover, total phenol and flavonoid contents were determined using appropriate methods.

Results: Rats treated with the extract showed a lower incidence of up to 50% in the pre-initiation higher dose, average number (p<0.05),and size (p<0.05) of tumours compared to untreated rats. It also inhibited colorectal cancer-associated increases in serum total cholesterol and triglycerides. The extract's IC50 value in the MTT assay was found to be higher than 200 µg/mL. The extract had an IC50 of 74.88 ± 0.86 µg/mL and 84.69 ± 2.02 µg/mL in the reducing power and DPPH assays, respectively. Total flavonoid and phenol contents were 14.51 ± 0.41 mg quercetin acid equivalent/gm and 47.37 ± 0.72 mg gallic acid equivalent/gm of the crude extract, respectively.

Conclusion: The findings collectively indicated that the leaves of V. auriculifera possess chemopreventive activity, probably mediated through antioxidant mechanisms, which supports the traditional claim.

背景:Vernonia auriculifera Hiern(菊科)是埃塞俄比亚的一种草药,传统上用于治疗皮肤癌和胃肠道癌症。本研究调查了枳实叶提取物对二甲基肼(DMH)诱导的大鼠结直肠癌发生的化学预防潜力:方法:将大鼠分为九组(正常对照组、阳性对照组和阴性对照组,以及三个启动前组和三个启动后组)。除正常对照组(给予 1 mL/100 g 蒸馏水)外,其余八组连续 15 周腹腔注射 DMH(20 mg/kg)以诱发大肠肿瘤。在诱发癌症前后,分别按 100、200 和 400 毫克/千克的剂量给诱发前组和诱发后组口服提取物。阳性对照组在整个实验期间口服阿司匹林(60 毫克/千克/天)。测定的参数包括体重、肿瘤平均数量、大小、进展、发病率、总胆固醇、血清总蛋白和甘油三酯水平。采用 MTT 法评估了提取物在 Caco-2 细胞中的细胞毒性活性,还采用 2.2-二苯基-1-苦基肼(DPPH)和还原力法评估了提取物的抗氧化活性。此外,还采用适当的方法测定了总酚和类黄酮的含量:用该提取物处理的大鼠在启动前的较高剂量下发病率降低了 50%,MTT 试验中的平均值(pp50 值)高于 200 µg/mL。在还原力和 DPPH 试验中,提取物的 IC50 分别为 74.88 ± 0.86 µg/mL 和 84.69 ± 2.02 µg/mL。总黄酮和酚含量分别为 14.51 ± 0.41 毫克槲皮素酸当量/克米和 47.37 ± 0.72 毫克没食子酸当量/克米:研究结果综合表明,枳实叶具有化学预防活性,可能是通过抗氧化机制介导的,这支持了传统的说法。
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引用次数: 0
Anti-Convulsant Activity of Soxhlet Leaf Extracts of Ajuga Integrifolia Buch.-Ham. Ex D.Don (Lamiaceae) in Mice. 砂仁索叶提取物的抗惊厥活性-火腿Ex D.Don(Lamiaceae)在小鼠中。
Q2 Medicine Pub Date : 2023-05-30 eCollection Date: 2023-01-01 DOI: 10.2147/JEP.S409099
Tesfaye Desalegn, Ephrem Engidawork

Background: The leaves of Ajuga integrifolia Buch.-Ham. ex D.Don (Lamiaceae) have long been used as an anti-convulsant remedy in Ethiopian traditional medicine. However, the evidence supporting their use is sparse in the literature. This study was conducted to add to the existing body of knowledge about the anti-convulsant activity of the plant.

Methods: The anti-convulsant activity of the extract was investigated in both acute (pentylenetetrazol [PTZ], 80 mg/kg; and maximal electroshock [MES]) and chronic (PTZ, 35 mg/kg) kindling seizure models. For the experimental paradigms, various doses of the extract (100, 200, and 400 mg/kg) were administered. Positive controls received sodium valproate (200 mg/kg) for the PTZ model and phenytoin (25 mg/kg) for the MES model. Parameters including the onset of clonus and duration of hindlimb tonic extension were recorded and compared with controls. Moreover, the total alkaloid, flavonoid, and phenol contents of the extracts were determined.

Results: Ethyl acetate extract produced a superior effect among all solvent extracts in both the PTZ and MES models. At all doses, it significantly delayed the mean onset of clonus (p<0.01) in the PTZ test compared to controls. It also significantly reduced (p<0.001) the mean duration of hindlimb tonic extension in the MES model. Treatment of mice with 200 mg/kg (p<0.01) and 400 mg/kg (p<0.001) of ethyl acetate extract significantly protected against PTZ-induced kindling compared to controls. The leaf was found to contain 10.002±0.119 mg atropine equivalent per gram of dry extract of alkaloids, 9.045±0.8445 mg quercetin equivalent per gram of dry extract of flavonoids, and 21.928±1.118 mg gallic acid equivalent per gram of dry extract of phenols.

Conclusion: This study indicated that the plant A. integrifolia has anti-convulsant activity in both acute and chronic models of seizure. This plant represents a potential source for the development of a new anti-epileptic drug for pharmacoresistant epilepsy.

背景:整叶白鲸的叶子-火腿在埃塞俄比亚传统医学中,老唐(Lamiaceae)长期被用作抗惊厥药物。然而,支持其使用的证据在文献中很少。进行这项研究是为了增加有关该植物抗惊厥活性的现有知识。方法:研究该提取物在急性(戊四氮,80mg/kg;最大电击[MES])和慢性(戊四唑,35mg/kg)点燃癫痫模型中的抗惊厥活性。对于实验范例,给予不同剂量的提取物(100、200和400mg/kg)。阳性对照组接受丙戊酸钠(200 mg/kg)用于PTZ模型,接受苯妥英钠(25 mg/kg)用于MES模型。记录包括阵挛发作和后肢强直性伸展持续时间在内的参数,并与对照组进行比较。此外,还测定了提取物中总生物碱、黄酮和酚的含量。结果:在PTZ和MES模型中,乙酸乙酯提取物的效果优于所有溶剂提取物。在所有剂量下,它都能显著延迟阵挛的平均发作(pppp)。结论:本研究表明,整叶A.integrifolia植物在急性和慢性癫痫发作模型中都具有抗惊厥活性。该植物为开发一种新的抗癫痫药物来治疗耐药性癫痫提供了潜在的来源。
{"title":"Anti-Convulsant Activity of Soxhlet Leaf Extracts of <i>Ajuga Integrifolia</i> Buch.-Ham. Ex D.Don (Lamiaceae) in Mice.","authors":"Tesfaye Desalegn,&nbsp;Ephrem Engidawork","doi":"10.2147/JEP.S409099","DOIUrl":"10.2147/JEP.S409099","url":null,"abstract":"<p><strong>Background: </strong>The leaves of <i>Ajuga integrifolia</i> Buch.-Ham. ex D.Don (Lamiaceae) have long been used as an anti-convulsant remedy in Ethiopian traditional medicine. However, the evidence supporting their use is sparse in the literature. This study was conducted to add to the existing body of knowledge about the anti-convulsant activity of the plant.</p><p><strong>Methods: </strong>The anti-convulsant activity of the extract was investigated in both acute (pentylenetetrazol [PTZ], 80 mg/kg; and maximal electroshock [MES]) and chronic (PTZ, 35 mg/kg) kindling seizure models. For the experimental paradigms, various doses of the extract (100, 200, and 400 mg/kg) were administered. Positive controls received sodium valproate (200 mg/kg) for the PTZ model and phenytoin (25 mg/kg) for the MES model. Parameters including the onset of clonus and duration of hindlimb tonic extension were recorded and compared with controls. Moreover, the total alkaloid, flavonoid, and phenol contents of the extracts were determined.</p><p><strong>Results: </strong>Ethyl acetate extract produced a superior effect among all solvent extracts in both the PTZ and MES models. At all doses, it significantly delayed the mean onset of clonus (<i>p</i><0.01) in the PTZ test compared to controls. It also significantly reduced (<i>p</i><0.001) the mean duration of hindlimb tonic extension in the MES model. Treatment of mice with 200 mg/kg (<i>p</i><0.01) and 400 mg/kg (<i>p</i><0.001) of ethyl acetate extract significantly protected against PTZ-induced kindling compared to controls. The leaf was found to contain 10.002±0.119 mg atropine equivalent per gram of dry extract of alkaloids, 9.045±0.8445 mg quercetin equivalent per gram of dry extract of flavonoids, and 21.928±1.118 mg gallic acid equivalent per gram of dry extract of phenols.</p><p><strong>Conclusion: </strong>This study indicated that the plant <i>A. integrifolia</i> has anti-convulsant activity in both acute and chronic models of seizure. This plant represents a potential source for the development of a new anti-epileptic drug for pharmacoresistant epilepsy.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"15 ","pages":"241-253"},"PeriodicalIF":0.0,"publicationDate":"2023-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/51/b0/jep-15-241.PMC10239258.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9584117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Antiulcer Effect of Aqueous Ethanolic Extracts of Pseudocedrela kotschyi (Schweinf) Harms (Meliaceae) and Ximenia americana L. (Olacaceae). Pseudocedrela kotschyi (Schweinf) Harms( Meliaceae)和 Ximenia americana L.(Olacaceae)乙醇水提取物的抗溃疡作用。
Q2 Medicine Pub Date : 2023-05-29 eCollection Date: 2023-01-01 DOI: 10.2147/JEP.S393168
Edwige T Delma, Moussa Ouédraogo, Aimé S Ouédraogo, Arsène W Nikiema, Moustapha Abdoulaye Gambo, Norbert Ramde, Estelle N H Youl, Assita Sanou-Lamien, Olga Mélanie Lompo, Pierre I Guissou

Purpose: This study aimed to provide pharmacological evidence of Pseudocedrela kotschyi and Ximenia americana in preventing or healing peptic ulcers claimed by traditional healers in Burkina Faso.

Methods: The trunk bark of Pseudocedrela kotschyi and the roots bark of Ximenia americana (Olacaceae) were macerated in mixed ethanol/water (80:20), respectively, to obtain dried extracts. Two models of hydrochloric acid (HCl, 0.3 M/ethanol, 60%) and hypothermic stress-induced peptic ulcer were used. The cytoprotective effect of individual or combined plant extracts was assessed at 1; 10; 30mg/kg. bw. Then, the healing effect of the extracts at 10mg/kg.bw was evaluated within 21 days of treatment on the hydrochloric acid-induced ulcer model. The extracts' antioxidant activity and phenolic content were assessed to support the plant extracts' efficiency.

Results: The extracts of P. kotschyi and X. americana at 10 mg/kg.bw reduced ulceration index in hydrochloric acid- and hypothermic stress-ulcer models by more than 83% and 65%, respectively. The extract from X. americana at 10mg/kg.bw allowed complete ulcer healing but not the association of the two plant extracts. The plant extracts had IC50of inhibition of DPPH radical lower than 5μg/mL and total ferric reducing antioxidant power of more than 77 mg EQAA/100mg. The total polyphenolic content was 64.82 ±0.99 and 53.75 ±1.39 mg EGA/g of dried extract of P. kotschyi and X. americana, respectively.

Conclusion: X. americana extract is better than the combined two plant extracts in gastric cytoprotection and ulcer healing. Further investigations are needed to highlight mechanism-based effects.

目的:本研究旨在提供布基纳法索传统治疗师声称的 Pseudocedrela kotschyi 和 Ximenia americana 在预防或治疗消化性溃疡方面的药理证据:方法:分别用乙醇/水(80:20)混合液浸泡Pseudocedrela kotschyi的树干皮和Ximenia americana(橄榄科植物)的根皮,获得干燥提取物。采用盐酸(HCl,0.3 M/乙醇,60%)和低温应激诱导消化性溃疡两种模型。分别以 1、10、30 毫克/千克体重的剂量评估单个或组合植物提取物的细胞保护作用。然后,在盐酸诱导的溃疡模型上,以 10 毫克/千克体重的提取物在治疗 21 天内的愈合效果进行了评估。此外,还评估了提取物的抗氧化活性和酚含量,以支持植物提取物的功效:结果:10 mg/kg.bw的P. kotschyi和X. americana提取物可使盐酸和低体温应激溃疡模型的溃疡指数分别降低83%和65%以上。10 毫克/千克体重的 X. americana 提取物能使溃疡完全愈合,而两种植物提取物的联合作用则不能使溃疡完全愈合。植物提取物抑制 DPPH 自由基的 IC50 低于 5μg/mL,总铁还原抗氧化能力超过 77 mg EQAA/100mg。P. kotschyi 和 X. americana 干提取物的总多酚含量分别为 64.82 ±0.99 和 53.75 ±1.39 mg EGA/g:结论:在胃细胞保护和溃疡愈合方面,X. americana 提取物优于两种植物提取物的组合。需要进一步研究以突出基于机制的作用。
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引用次数: 0
Anthocyanin-Containing Purple Sweet Potato (Ipomoea batatas L.) Synbiotic Yogurt Inhibited 3T3-L1 Adipogenesis by Suppressing White Adipocyte-Specific Genes. 含有花青素的紫甘薯(Ipomoea batatas L.)共生酸奶通过抑制白色脂肪细胞特异性基因抑制3T3-L1脂肪生成。
Q2 Medicine Pub Date : 2023-05-22 eCollection Date: 2023-01-01 DOI: 10.2147/JEP.S405433
Eko Fuji Ariyanto, Widad Aghnia Shalannandia, Uci Ary Lantika, Taufik Muhammad Fakih, Dwi Syah Fitra Ramadhan, Arini Nurisydayanti Gumilar, Farhan Khalil Permana, Anisa Nadia Rahmah, Nur Atik, Astrid Feinisa Khairani

Purpose: We unravel the effect of anthocyanin-containing purple sweet potato synbiotic yogurt (PSPY) on 3T3-L1 adipocyte differentiation and its fundamental molecular mechanisms.

Methods: Molecular docking simulation was performed to observe and identify the affinity and interaction between bioactive compounds and targeted proteins. MDI (isobutylmethylxanthine, dexamethasone, and insulin)-containing medium, a cocktail that stimulates adipogenesis, was used in this study. The toxic effect possibility of the yogurt product was evaluated using 3-[4, 5-dimethylthiazol-2-yl]-2.5 diphenyl tetrazolium bromide (MTT) assay. A 0.25%, 0.5%, 1%, and 5% (v/v) plain or purple sweet potato yogurt supernatant was given to 3T3-L1 preadipocyte culture medium from 24 h after seeding until day 11 of MDI-induced differentiation. The mRNA expression and lipid accumulation were analyzed using RT-qPCR and Oil red O staining, respectively, on day 11 after differentiation induction.

Results: In silico study suggested that anthocyanin-derived compounds have the potential to inhibit peroxisome proliferator activated receptor gamma (PPAR-γ), a master regulator for white adipogenesis. Anthocyanin-containing PSPY significantly suppressed the expression of Pparg, Adipoq, Slc2a4, and Pgc1a. PSPY significantly suppressed Pparg with 1% and 5% concentrations, while with a concentration of 0.25%, PSPY significantly suppressed Adipoq expression as compared to control. Significant inhibition of Slc2a4 and Pgc1a was observed starting from a 0.25% concentration of PSPY. The suppression of adipogenic genes was also observed with the treatment of plain yogurt; however, the effects were relatively lower than the PSPY. The group treated with 1% and 5% of PSPY also showed inhibition effects on lipid accumulation.

Conclusion: This study demonstrated PSPY inhibition effect on white adipocyte differentiation through suppression of Pparg and its downstream genes, Adipoq and Slc2a4, indicating the potential of this yogurt as a functional food for obesity management and prevention.

目的:探讨含花青素的紫甘薯合生酸奶(PSPY)对3T3-L1脂肪细胞分化的影响及其基本分子机制。方法:通过分子对接模拟,观察和鉴定生物活性化合物与靶蛋白之间的亲和力和相互作用。本研究中使用了含有MDI(异丁基甲基黄嘌呤、地塞米松和胰岛素)的培养基,这是一种刺激脂肪生成的混合物。使用3-[4,5-二甲基噻唑-2-基]-2.5二苯基溴化四氮唑(MTT)测定法评估酸奶产品的毒性作用可能性。从接种后24小时至MDI诱导分化的第11天,将0.25%、0.5%、1%和5%(v/v)的普通或紫甘薯酸奶上清液给予3T3-L1前脂肪细胞培养基。分化诱导后第11天,分别使用RT-qPCR和油红O染色分析mRNA表达和脂质积聚。结果:计算机研究表明,花青素衍生的化合物具有抑制过氧化物酶体增殖物激活受体γ(PPAR-γ)的潜力,PPAR-γ是白色脂肪生成的主要调节因子。含有PSPY的花青素显著抑制Pparg、Adipoq、Slc2a4和Pgc1a的表达。PSPY在1%和5%浓度下显著抑制Pparg,而在0.25%浓度下,与对照相比,PSPY显著抑制Adipoq的表达。从0.25%浓度的PSPY开始观察到对Slc2a4和Pgc1a的显著抑制。在纯酸奶的处理中也观察到了脂肪生成基因的抑制;然而,效果相对低于PSPY。用1%和5%PSPY处理的组也显示出对脂质积聚的抑制作用。结论:本研究通过抑制Pparg及其下游基因Adipoq和Slc2a4,证明了PSPY对白色脂肪细胞分化的抑制作用,表明该酸奶具有作为肥胖管理和预防功能性食品的潜力。
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引用次数: 0
Pharmacological Evaluation of the Anesthetic and Analgesic Potential of Injection Harsha 22: A Novel Polyherbal Local Anesthetic Formulation Intended for Parenteral Administration in Wistar Albino Rats. 注射用哈沙 22 的麻醉和镇痛潜力药理评估:一种用于 Wistar 白化大鼠肠外给药的新型多草本局部麻醉剂配方。
Q2 Medicine Pub Date : 2023-03-27 eCollection Date: 2023-01-01 DOI: 10.2147/JEP.S402277
Shan Sasidharan, Asha Nair Kaveri, M S Sithara, Hareendran Nair J

Background: Local anaesthetics are medications that cause numbness that can be reversed by applying them topically. Local anaesthetics are clinically used to control pain during minor surgeries or to treat other acute and chronic pain. The present investigation intended to investigate the anesthetic as well as analgesic potential of Injection Harsha 22, a novel polyherbal formulation in Wistar albino rats.

Methods: The anesthetic potential of Injection Harsha 22 was evaluated by a heat tail-flick latency (TFL) test, whereas the analgesic effect was elevated by electrical stimulation testing. Here, lignocaine (2%) was used as the standard anesthetic drug.

Results: In TFL, Injection Harsha 22 showed anesthetic effects up to 90 minutes after application. Also, the duration of anesthesia in rats that were administered subcutaneously with Injection Harsha 22 was comparable to that of the rats treated with commercial lignocaine (2%). In an electrical stimulation test, single administration of Injection Harsha 22 to rats significantly prolonged analgesia compared with the normal control group. The median duration of analgesia in rats administered subcutaneously with Injection Harsha 22 and lignocaine solution was 40 minutes and 35 minutes, respectively. Furthermore, Injection Harsha 22 does not interfere with the hematopoietic system of the experiment animals.

Conclusion: Thus, the present investigation established the in vivo anesthetic and analgesic potential of Injection Harsha 22 in experimental animals. Hence, it can be concluded that Injection Harsha 22 can become a prominent substitute for lignocaine as a local anaesthetic agent after establishing its efficacy through stringent clinical trials in humans.

背景:局部麻醉剂是一种可导致麻木的药物,局部使用可使麻木逆转。局部麻醉剂在临床上用于控制小手术中的疼痛或治疗其他急性和慢性疼痛。本研究旨在调查哈沙 22 注射液这种新型多草药制剂对 Wistar 白化大鼠的麻醉和镇痛潜力:方法:注射用哈沙 22 的麻醉潜力通过热触尾潜伏期(TFL)试验进行评估,而镇痛效果则通过电刺激试验进行评估。这里使用木质素卡因(2%)作为标准麻醉药物:结果:在 TFL 试验中,注射用哈沙 22 的麻醉效果可持续到使用后 90 分钟。此外,皮下注射哈沙 22 的大鼠的麻醉持续时间与使用商品木质素卡因(2%)的大鼠相当。在电刺激试验中,与正常对照组相比,大鼠单次注射哈沙 22 可显著延长镇痛时间。大鼠皮下注射哈沙 22 和木质素溶液的中位镇痛持续时间分别为 40 分钟和 35 分钟。此外,注射用哈沙 22 不会干扰实验动物的造血系统:因此,本研究证实了注射用哈沙 22 在实验动物体内的麻醉和镇痛潜力。因此,可以得出结论,在通过严格的人体临床试验确定其疗效后,注射用哈沙 22 可以成为木质素局部麻醉剂的主要替代品。
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引用次数: 0
期刊
Journal of Experimental Pharmacology
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