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Mechanistic insights into Ageratum conyzoides L. in preventing spontaneous abortion: A computational and pharmacological study
Pub Date : 2025-01-10 DOI: 10.1016/j.prenap.2025.100143
A.A. Ekozin , O.B. Isola , O.H. Onyijen , R.T. Omojoyegbe , K.E. Enerijiofi , E.O. Olaitan
Spontaneous abortion (SA) imposes significant physical, psychological, and economic burdens on affected families. This study employs network pharmacology and HPLC-MS analysis to investigate the therapeutic mechanisms of Ageratum conyzoides L. in the treatment of SA. Using HPLC-MS, we identified a diverse array of bioactive compounds in Ageratum conyzoides L., including diterpenoid alkaloids (aconitine, mesaconitine, hypaconitine), sesquiterpene lactones (levistilide A), nucleosides (inosine), coumarin derivatives (ligustilide), triterpenoids, and phenolic acids. These compounds were confirmed through retention times and mass spectrometry fragmentation patterns. Network pharmacology analysis identified 27 active components from the plant's secondary metabolites and revealed 514 related targets. In total, 2197 potential targets related to SA were identified, with 220 shared between the plant and disease. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis identified 196 pathways, including the PI3K-Akt and cancer-related pathways. Molecular docking further confirmed the interactions between major compounds (quercetin, kaempferol, isorhamnetin) and key targets, such as MAPK1 and MAPK3, with strong binding affinities. Pharmacological evaluation showed that Ageratum conyzoides L. corrected Th cell imbalance by inhibiting Th2 cell differentiation, increasing the Th1/Th2 ratio, and enhancing T-bet gene expression. Serum progesterone levels significantly decreased post-abortion. Flow cytometry revealed restored Th1/Th2 differentiation, while qPCR and immunohistochemical analyses confirmed upregulation of T-bet and inhibition of GATA-3 and IL-4 expression. The extract's efficacy was confirmed across multiple experimental groups using ANOVA and Bonferroni post-hoc tests. This study highlights Ageratum conyzoides L.'s potential as a multifaceted therapeutic agent for SA, supported by its comprehensive molecular profile, revealed through HPLC-MS and network pharmacology.
{"title":"Mechanistic insights into Ageratum conyzoides L. in preventing spontaneous abortion: A computational and pharmacological study","authors":"A.A. Ekozin ,&nbsp;O.B. Isola ,&nbsp;O.H. Onyijen ,&nbsp;R.T. Omojoyegbe ,&nbsp;K.E. Enerijiofi ,&nbsp;E.O. Olaitan","doi":"10.1016/j.prenap.2025.100143","DOIUrl":"10.1016/j.prenap.2025.100143","url":null,"abstract":"<div><div>Spontaneous abortion (SA) imposes significant physical, psychological, and economic burdens on affected families. This study employs network pharmacology and HPLC-MS analysis to investigate the therapeutic mechanisms of <em>Ageratum conyzoides</em> L. in the treatment of SA. Using HPLC-MS, we identified a diverse array of bioactive compounds in <em>Ageratum conyzoides</em> L., including diterpenoid alkaloids (aconitine, mesaconitine, hypaconitine), sesquiterpene lactones (levistilide A), nucleosides (inosine), coumarin derivatives (ligustilide), triterpenoids, and phenolic acids. These compounds were confirmed through retention times and mass spectrometry fragmentation patterns. Network pharmacology analysis identified 27 active components from the plant's secondary metabolites and revealed 514 related targets. In total, 2197 potential targets related to SA were identified, with 220 shared between the plant and disease. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis identified 196 pathways, including the PI3K-Akt and cancer-related pathways. Molecular docking further confirmed the interactions between major compounds (quercetin, kaempferol, isorhamnetin) and key targets, such as MAPK1 and MAPK3, with strong binding affinities. Pharmacological evaluation showed that <em>Ageratum conyzoides</em> L. corrected Th cell imbalance by inhibiting Th2 cell differentiation, increasing the Th1/Th2 ratio, and enhancing T-bet gene expression. Serum progesterone levels significantly decreased post-abortion. Flow cytometry revealed restored Th1/Th2 differentiation, while qPCR and immunohistochemical analyses confirmed upregulation of T-bet and inhibition of GATA-3 and IL-4 expression. The extract's efficacy was confirmed across multiple experimental groups using ANOVA and Bonferroni post-hoc tests. This study highlights <em>Ageratum conyzoides</em> L.'s potential as a multifaceted therapeutic agent for SA, supported by its comprehensive molecular profile, revealed through HPLC-MS and network pharmacology.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"6 ","pages":"Article 100143"},"PeriodicalIF":0.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143156802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
GC-MS identified bioactive compounds of Urena lobata L. demonstrate anti–inflammatory and immunomodulatory potentials against rheumatoid arthritis: An in silico, in vitro and in vivo evaluation
Pub Date : 2025-01-10 DOI: 10.1016/j.prenap.2025.100152
Dinesh Kumar , Somendra Kumar , Motiram Sahu , Gift Crucifix Pender , Chandramohan Govindasamy , Sanjit Kumar , Anil Kumar
Rheumatoid arthritis (RA) is a chronic and disabling multisystem disease that progresses over time, leading to pain, swelling, and stiffness in the synovial joints. The specific cause of RA is not fully understood, but it is classified as a systemic autoimmune disorder. This study evaluated the anti-rheumatoid activities of bioactive compounds from the leaf extract of Urena lobataL through in silico predictions. We studied the leaf of Urena lobata L. and analyzed its ethyl-acetate-based leaf extract using GC-MS, detected potential compounds against target proteins, and performed docking by chimera with Lipinski rule and ADME validation by SwissADME analysis. In the GC-MS analysis, we identified 42 compounds of which 34 were first-time reporting, and many of them with significant biological activities. Squalene and Heptadecane, 2,6,10,15-tetramethyl- were identified as potential lead compounds in our docking analysis against TNF-alpha and COX-2, and squalene was found most suitable compound compared to Heptadecane, 2,6,10,15-tetramethyl-, because Heptadecane, 2,6,10,15-tetramethyl- was detected as P-glycoprotein (Pgp) substrate. In in vivo confirmation we found that Paw volume, Cytokine TNF-alpha, and IL-6 have confirmed the efficacy of extract of U. lobata in rats against Rheumatoid arthritis.
{"title":"GC-MS identified bioactive compounds of Urena lobata L. demonstrate anti–inflammatory and immunomodulatory potentials against rheumatoid arthritis: An in silico, in vitro and in vivo evaluation","authors":"Dinesh Kumar ,&nbsp;Somendra Kumar ,&nbsp;Motiram Sahu ,&nbsp;Gift Crucifix Pender ,&nbsp;Chandramohan Govindasamy ,&nbsp;Sanjit Kumar ,&nbsp;Anil Kumar","doi":"10.1016/j.prenap.2025.100152","DOIUrl":"10.1016/j.prenap.2025.100152","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic and disabling multisystem disease that progresses over time, leading to pain, swelling, and stiffness in the synovial joints. The specific cause of RA is not fully understood, but it is classified as a systemic autoimmune disorder. This study evaluated the anti-rheumatoid activities of bioactive compounds from the leaf extract of <em>Urena lobata</em>L through <em>in silico</em> predictions. We studied the leaf of <em>Urena lobata</em> L. and analyzed its ethyl-acetate-based leaf extract using GC-MS, detected potential compounds against target proteins, and performed docking by chimera with Lipinski rule and ADME validation by SwissADME analysis. In the GC-MS analysis, we identified 42 compounds of which 34 were first-time reporting, and many of them with significant biological activities. Squalene and Heptadecane, 2,6,10,15-tetramethyl- were identified as potential lead compounds in our docking analysis against TNF-alpha and COX-2, and squalene was found most suitable compound compared to Heptadecane, 2,6,10,15-tetramethyl-, because Heptadecane, 2,6,10,15-tetramethyl- was detected as P-glycoprotein (Pgp) substrate. In <em>in vivo</em> confirmation we found that Paw volume, Cytokine TNF-alpha, and IL-6 have confirmed the efficacy of extract of <em>U. lobata</em> in rats against Rheumatoid arthritis.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"6 ","pages":"Article 100152"},"PeriodicalIF":0.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143156842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
In vitro antioxidant and antiarthritic effects of Persicaria lanigera R. Br. Soják (Polygonaceae) leaf extract in complete Freund’s Adjuvant-induced rheumatoid arthritis model via immunomodulatory regulation of NF-κB, IL-1β, TNF-α, and COX-2 signaling pathways
Pub Date : 2025-01-09 DOI: 10.1016/j.prenap.2025.100151
Meshack Antwi-Adjei , Benjamin Aboagye , Ernest Obese , Elvis Ofori Ameyaw , Emmanuel Awintiig Adakudugu , Benjamin Amoani , Yakubu Jibira , Roberta Antwi-Adjei , George Owusu , Daniel Anokwah

Background

Rheumatoid arthritis is an autoimmune disease with a high prevalence rate globally, particularly in developing countries. Persicaria lanigera is used in folkloric medicine to treat arthritis and other inflammatory disorders.

Objective

The present study appraises the potential antioxidant activity and management of arthritis using aqueous ethanol leaf extract of Persicaria lanigera in a CFA-induced arthritis model.

Materials and methods

The ex-vivo antioxidant activity of the extract was carried out in TAC, DPPH, and H2O2 experiments. Furthermore, in a CFA-induced arthritis model, the antiarthritic effect of Persicaria lanigera extract (100–600 mg kg−1, p.o.) was studied by intraplantar injection of 100 µl CFA into right hind limbs of Sprague-Dawley rats (n = 7).

Results

In this study, P. lanigera exhibited an increase of 39.13 ± 6.80 µg ascorbic acid equivalent per g in TAC and exerted high scavenging effects of 81.87 ± 8.25 % and 0.03 ± 0.01 (p < 0.05) when compared to ascorbic acid in DPPH and H2O2 respectively. In the CFA-induced model, P. lanigera extract substantially lowered the mean percentage maximal arthritic paw from 854.50 ± 67.00 % to 568.50 ± 91.18 %, 545.50 ± 71.88 % and 541.83 ± 70.21 % (p < 0.05) at 100, 300, and 600 mg/kg when given therapeutically, respectively. In addition, P. lanigera extract reduced the total inflamed arthritic paw formed significantly by 20.98 %, 27.11 %, and 33.45 % (p < 0.05) at the same doses, respectively. The haematological and biochemical alterations were restored by the extract and weight loss in arthritic rats was prevented. In the histopathological and radiological assessments, P. lanigera extract improved the condition of the ankle joint, inhibited bone and cartilage erosion, and maintained the integrity of bone tissues. Furthermore, P. lanigera extract inhibited NF-κB, IL-1β, TNF-α, and COX-2 signaling pathways, and improved ocular conditions of the arthritic rats.

Discussion

The findings have a relevant impact on the development of newer and alternative treatment sources for the management of rheumatoid arthritis as well as other related chronic inflammatory disorders. Ultimately, this study provides vital scientific evidence to support the folkloric use of the plant in traditional medicine for treating inflammatory diseases.

Conclusion

Persicaria lanigera extract possesses antioxidant and arthritic properties.
{"title":"In vitro antioxidant and antiarthritic effects of Persicaria lanigera R. Br. Soják (Polygonaceae) leaf extract in complete Freund’s Adjuvant-induced rheumatoid arthritis model via immunomodulatory regulation of NF-κB, IL-1β, TNF-α, and COX-2 signaling pathways","authors":"Meshack Antwi-Adjei ,&nbsp;Benjamin Aboagye ,&nbsp;Ernest Obese ,&nbsp;Elvis Ofori Ameyaw ,&nbsp;Emmanuel Awintiig Adakudugu ,&nbsp;Benjamin Amoani ,&nbsp;Yakubu Jibira ,&nbsp;Roberta Antwi-Adjei ,&nbsp;George Owusu ,&nbsp;Daniel Anokwah","doi":"10.1016/j.prenap.2025.100151","DOIUrl":"10.1016/j.prenap.2025.100151","url":null,"abstract":"<div><h3>Background</h3><div>Rheumatoid arthritis is an autoimmune disease with a high prevalence rate globally, particularly in developing countries. <em>Persicaria lanigera</em> is used in folkloric medicine to treat arthritis and other inflammatory disorders.</div></div><div><h3>Objective</h3><div>The present study appraises the potential antioxidant activity and management of arthritis using aqueous ethanol leaf extract of <em>Persicaria lanigera</em> in a CFA-induced arthritis model.</div></div><div><h3>Materials and methods</h3><div>The <em>ex-vivo</em> antioxidant activity of the extract was carried out in TAC, DPPH, and H<sub>2</sub>O<sub>2</sub> experiments. Furthermore, in a CFA-induced arthritis model, the antiarthritic effect of <em>Persicaria lanigera</em> extract (100–600 mg kg<sup>−1</sup>, <em>p.o.</em>) was studied by intraplantar injection of 100 µl CFA into right hind limbs of Sprague-Dawley rats (n = 7).</div></div><div><h3>Results</h3><div>In this study, <em>P. lanigera</em> exhibited an increase of 39.13 ± 6.80 µg ascorbic acid equivalent per g in TAC and exerted high scavenging effects of 81.87 ± 8.25 % and 0.03 ± 0.01 (<em>p &lt; 0.05</em>) when compared to ascorbic acid in DPPH and H<sub>2</sub>O<sub>2</sub> respectively. In the CFA-induced model, <em>P. lanigera</em> extract substantially lowered the mean percentage maximal arthritic paw from 854.50 ± 67.00 % to 568.50 ± 91.18 %, 545.50 ± 71.88 % and 541.83 ± 70.21 % (<em>p &lt; 0.05</em>) at 100, 300, and 600 mg/kg when given therapeutically, respectively. In addition, <em>P. lanigera</em> extract reduced the total inflamed arthritic paw formed significantly by 20.98 %, 27.11 %, and 33.45 % (<em>p &lt; 0.05</em>) at the same doses, respectively. The haematological and biochemical alterations were restored by the extract and weight loss in arthritic rats was prevented. In the histopathological and radiological assessments, <em>P. lanigera</em> extract improved the condition of the ankle joint, inhibited bone and cartilage erosion, and maintained the integrity of bone tissues. Furthermore, <em>P. lanigera</em> extract inhibited NF-κB, IL-1β, TNF-α, and COX-2 signaling pathways, and improved ocular conditions of the arthritic rats.</div></div><div><h3>Discussion</h3><div>The findings have a relevant impact on the development of newer and alternative treatment sources for the management of rheumatoid arthritis as well as other related chronic inflammatory disorders. Ultimately, this study provides vital scientific evidence to support the folkloric use of the plant in traditional medicine for treating inflammatory diseases.</div></div><div><h3>Conclusion</h3><div><em>Persicaria lanigera</em> extract possesses antioxidant and arthritic properties.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"6 ","pages":"Article 100151"},"PeriodicalIF":0.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143156839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Thymoquinone inhibits adipocyte development in 3T3-L1 cells system by modulating the AKT and AMPK signaling pathways
Pub Date : 2025-01-09 DOI: 10.1016/j.prenap.2025.100149
Shamima Ahmed , Yuki Nishigaki , Mohammad Shaokat Ali , Isao Matsui-Yuasa , Akiko Kojima-Yuasa

Aims

Obesity, a major global health concern, leads to various metabolic disorders. Adipogenesis, the process of preadipocytes differentiating into mature adipocytes, is key to excessive lipid accumulation. This study examined the anti-obesity effects of thymoquinone (TQ), a compound from Nigella sativa seeds, using 3T3-L1 pre-adipocytes in vitro.

Main methods

Cell viability was assessed with the neutral red assay. Lipid accumulation and GPDH activity were evaluated using oil red O staining and the Wise and Green method, respectively. Reactive oxygen species levels were quantified with the DCFH-DA method, while immunofluorescence staining was employed to examine the nuclear localization of C/EBPβ. The qRT-PCR and western blot assays were used to analyze the adipogenic and lipogenic markers.

Key findings

TQ inhibited lipid accumulation at concentrations of 6–30 µM without affecting cell viability. It also suppressed adipogenic transcription factors (PPARγ, C/EBPα, C/EBPβ, and SREBP-1c) and lipogenic genes (AdipoQ, FABP4, FAS, and ACC1). Additionally, TQ inhibited the AKT pathway and enhanced AMPK phosphorylation.

Significance

The results suggest that thymoquinone has anti-obesity properties by inhibiting adipogenic transcription factors and lipogenic genes through the regulation of AKT and AMPK pathways. Consequently, it could serve as a potential therapeutic agent for obesity.
{"title":"Thymoquinone inhibits adipocyte development in 3T3-L1 cells system by modulating the AKT and AMPK signaling pathways","authors":"Shamima Ahmed ,&nbsp;Yuki Nishigaki ,&nbsp;Mohammad Shaokat Ali ,&nbsp;Isao Matsui-Yuasa ,&nbsp;Akiko Kojima-Yuasa","doi":"10.1016/j.prenap.2025.100149","DOIUrl":"10.1016/j.prenap.2025.100149","url":null,"abstract":"<div><h3>Aims</h3><div>Obesity, a major global health concern, leads to various metabolic disorders. Adipogenesis, the process of preadipocytes differentiating into mature adipocytes, is key to excessive lipid accumulation. This study examined the anti-obesity effects of thymoquinone (TQ), a compound from <em>Nigella sativa</em> seeds, using 3T3-L1 pre-adipocytes <em>in vitro.</em></div></div><div><h3>Main methods</h3><div>Cell viability was assessed with the neutral red assay. Lipid accumulation and GPDH activity were evaluated using oil red O staining and the Wise and Green method, respectively. Reactive oxygen species levels were quantified with the DCFH-DA method, while immunofluorescence staining was employed to examine the nuclear localization of C/EBPβ. The qRT-PCR and western blot assays were used to analyze the adipogenic and lipogenic markers.</div></div><div><h3>Key findings</h3><div>TQ inhibited lipid accumulation at concentrations of 6–30 µM without affecting cell viability. It also suppressed adipogenic transcription factors (PPARγ, C/EBPα, C/EBPβ, and SREBP-1c) and lipogenic genes (<em>AdipoQ, FABP4, FAS, and ACC1</em>). Additionally, TQ inhibited the AKT pathway and enhanced AMPK phosphorylation.</div></div><div><h3>Significance</h3><div>The results suggest that thymoquinone has anti-obesity properties by inhibiting adipogenic transcription factors and lipogenic genes through the regulation of AKT and AMPK pathways. Consequently, it could serve as a potential therapeutic agent for obesity.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"6 ","pages":"Article 100149"},"PeriodicalIF":0.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143156837","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
Melatonin’s role in redox homeostasis: A preclinical and clinical perspective
Pub Date : 2025-01-07 DOI: 10.1016/j.prenap.2025.100147
Flaviene Felix Torres , Victoria Simões Bernardo , Ana Clara Albertin Zucão , Lucas Gazarini , Russel Joseph Reiter , Danilo Grünig Humberto da Silva
Melatonin is a phylogenetically ancient molecule with diverse biological activities, including anti-inflammatory and redox properties. Although its role as an antioxidant is well-established, the broader impact of melatonin on redox signaling pathways still needs to be explored. This review addresses this gap by providing an overview of melatonin's known mechanisms of action in major redox signaling pathways, such as Nrf2, NF-kB, and FoxO, as well as its involvement in epigenetic processes and the ubiquitin-proteasome system. The review also explores melatonin’s potential as a therapeutic agent in various pathological conditions, including cancer, Alzheimer’s disease, diabetes, and cardiomyopathy. Finally, we discuss recent clinical trials that underscore melatonin’s role in modulating hormesis-related redox signaling, suggesting its utility as a therapeutic adjuvant in diseases characterized by oxidative or inflammatory damage.
{"title":"Melatonin’s role in redox homeostasis: A preclinical and clinical perspective","authors":"Flaviene Felix Torres ,&nbsp;Victoria Simões Bernardo ,&nbsp;Ana Clara Albertin Zucão ,&nbsp;Lucas Gazarini ,&nbsp;Russel Joseph Reiter ,&nbsp;Danilo Grünig Humberto da Silva","doi":"10.1016/j.prenap.2025.100147","DOIUrl":"10.1016/j.prenap.2025.100147","url":null,"abstract":"<div><div>Melatonin is a phylogenetically ancient molecule with diverse biological activities, including anti-inflammatory and redox properties. Although its role as an antioxidant is well-established, the broader impact of melatonin on redox signaling pathways still needs to be explored. This review addresses this gap by providing an overview of melatonin's known mechanisms of action in major redox signaling pathways, such as Nrf2, NF-kB, and FoxO, as well as its involvement in epigenetic processes and the ubiquitin-proteasome system. The review also explores melatonin’s potential as a therapeutic agent in various pathological conditions, including cancer, Alzheimer’s disease, diabetes, and cardiomyopathy. Finally, we discuss recent clinical trials that underscore melatonin’s role in modulating hormesis-related redox signaling, suggesting its utility as a therapeutic adjuvant in diseases characterized by oxidative or inflammatory damage.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"6 ","pages":"Article 100147"},"PeriodicalIF":0.0,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143155959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
HPLC profile, biochemical and histoarchitectural changes in loperamide-induced constipated Wistar rats after oral administration of aqueous extract of Cnestis ferruginea (Vahl ex DC) roots
Pub Date : 2025-01-07 DOI: 10.1016/j.prenap.2025.100144
Musa Toyin Yakubu , Moses Dele Adams

Introduction

Aqueous extract of Cnestis ferruginea roots (AECFR) have been documented to exhibit laxative activity with no information on biochemical and histoarchitectural changes that accompany such treatments. Hence, this study was aimed at determining the biochemical and histoarchitectural alterations in constipated rats after treatment with AECFR.

Methodology

Sixty, healthy, Wistar rats (150.30 ± 3.52 g) were completely randomized into six groups (A-F; n = 10/group). Animals in group A (sham control, SC) received distilled water (DW) whilst constipated (induced with 3 daily doses of loperamide (LPD, 3 mg/kg body weight, BW) rats in groups B (negative control, NC), C (positive control, PC), D, E and F were orally gavaged at same point time with DW, bisacodyl (BCL, referenced cathartics, 25 mg/kg BW), AECFR at 25, 50 and 100 mg/kg BW, respectively, once daily for 7 days. Biochemical and histoarchitectural analyses/examinations and High Performance Liquid Chromatography (HPLC) profiling of AECFR were done using standard methods.

Results

The LPD-treatment related significant (p < 0.05) increases in liver ACP, liver and serum GGT, stomach and small intestine (SI) ALP, kidney AST, serum albumin (SALB), uric acid, urea, creatinine, TC, TAG, LDL-C and Cl- were further sustained by AECFR and BCL. In contrast, the LPD-treatment related decreases in stomach ACP, serum globulin (SGB), total bilirubin (TB) and conjugated bilirubin (CB) were also reduced (p < 0.05) by the AECFR and BCL. Furthermore, the increases in the activities/levels of liver, kidney and serum ALP, liver and serum ALT, SI and serum ACP and HDL-C were reduced (p < 0.05) by the AECFR and BCL whereas the LPD-treatment related decreases in the activity/levels of kidney ALT, Na+, K+ and AI were increased after treatment with AECFR and BCL. In all, the alterations did not compare (p > 0.05) favourably with the SC. Also, there were no treatment-related histoarchitectural changes in all the tissues. Ten chemical compounds were detected in AECFR with cephatonine (30.96 µg/100 g) and stepharanine (0.13 µg/100 g) being the most and the least abundant respectively.

Conclusion

The LPD, AECFR and BCL caused similar trend of damage and/or cellular dysfunction to the liver, kidney, stomach and small intestine of rats with no evidence of histoarchitectural distortion in all the tissues.
{"title":"HPLC profile, biochemical and histoarchitectural changes in loperamide-induced constipated Wistar rats after oral administration of aqueous extract of Cnestis ferruginea (Vahl ex DC) roots","authors":"Musa Toyin Yakubu ,&nbsp;Moses Dele Adams","doi":"10.1016/j.prenap.2025.100144","DOIUrl":"10.1016/j.prenap.2025.100144","url":null,"abstract":"<div><h3>Introduction</h3><div>Aqueous extract of <em>Cnestis ferruginea</em> roots (AECFR) have been documented to exhibit laxative activity with no information on biochemical and histoarchitectural changes that accompany such treatments. Hence, this study was aimed at determining the biochemical and histoarchitectural alterations in constipated rats after treatment with AECFR.</div></div><div><h3>Methodology</h3><div>Sixty, healthy, Wistar rats (150.30 ± 3.52 g) were completely randomized into six groups (A-F; n = 10/group). Animals in group A (sham control, SC) received distilled water (DW) whilst constipated (induced with 3 daily doses of loperamide (LPD, 3 mg/kg body weight, BW) rats in groups B (negative control, NC), C (positive control, PC), D, E and F were orally gavaged at same point time with DW, bisacodyl (BCL, referenced cathartics, 25 mg/kg BW), AECFR at 25, 50 and 100 mg/kg BW, respectively, once daily for 7 days. Biochemical and histoarchitectural analyses/examinations and High Performance Liquid Chromatography (HPLC) profiling of AECFR were done using standard methods.</div></div><div><h3>Results</h3><div>The LPD-treatment related significant (<em>p</em> &lt; 0.05) increases in liver ACP, liver and serum GGT, stomach and small intestine (SI) ALP, kidney AST, serum albumin (SALB), uric acid, urea, creatinine, TC, TAG, LDL-C and Cl<sup>-</sup> were further sustained by AECFR and BCL. In contrast, the LPD-treatment related decreases in stomach ACP, serum globulin (SGB), total bilirubin (TB) and conjugated bilirubin (CB) were also reduced (<em>p</em> &lt; 0.05) by the AECFR and BCL. Furthermore, the increases in the activities/levels of liver, kidney and serum ALP, liver and serum ALT, SI and serum ACP and HDL-C were reduced (<em>p</em> &lt; 0.05) by the AECFR and BCL whereas the LPD-treatment related decreases in the activity/levels of kidney ALT, Na<sup>+</sup>, K<sup>+</sup> and AI were increased after treatment with AECFR and BCL. In all, the alterations did not compare (<em>p</em> &gt; 0.05) favourably with the SC. Also, there were no treatment-related histoarchitectural changes in all the tissues. Ten chemical compounds were detected in AECFR with cephatonine (30.96 µg/100 g) and stepharanine (0.13 µg/100 g) being the most and the least abundant respectively.</div></div><div><h3>Conclusion</h3><div>The LPD, AECFR and BCL caused similar trend of damage and/or cellular dysfunction to the liver, kidney, stomach and small intestine of rats with no evidence of histoarchitectural distortion in all the tissues.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"6 ","pages":"Article 100144"},"PeriodicalIF":0.0,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143155960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ficus exasperata N-hexane-ethyl acetate extract inhibits lipoxygenase and protects against CCl4 – Induced TNF-α upregulation in Female Wistar Rats
Pub Date : 2025-01-07 DOI: 10.1016/j.prenap.2025.100148
Dorcas Ibukun Akinloye , Adio Jamiu Akamo , Ceaser Antiya Moses , Abiodun Sunday Oyelakin , Theophilus Aghogho Jarikre , Toluwalase Ayobami Adeosun , Adewale Segun James , Ofem Effiom Eteng , Olayinka Adebola Eruola , Olatunbosun Samuel Sojinu

Background

The excessive production of tumour necrosis factor-alpha (TNF-α) and lipoxygenase activity can lead to various adverse health effects. Traditional Chinese Medicine (TCM) has long been used to promote optimal well-being due to its bioactive constituents. Thus, one of the plant ingredients in TCM must be tested.

Objectives

The research seeks to examine the in vitro lipoxygenase inhibitory effects of Ficus exasperata N-hexane-ethyl acetate extract (NHEAE) and its in vivo protective role against CCl4-induced TNF-α overexpression in female Wistar rats, utilising tissue damage biomarkers, the expression levels of TNF-α, interleukin 10 (IL-10), and nuclear factor kappa B (NF-kB), along with histopathological evaluations of the liver and kidneys and in vitro lipoxygenase inhibition as metrics.

Methods

Thirty-six female Wistar rats were assigned into groups A, B, C, D, E, and F (n = 6). Groups A and B were administered olive oil for fourteen days as a pretreatment. Groups C, D, E, and F received pretreatment with vitamin E at a dosage of 100 mg per kilogram body weight (kg bwt), NHEAE at a dosage of 100 mg/kg bwt, NHEAE at a dosage of 200 mg/kg bwt, and NHEAE at a dosage of 200 mg/kg bwt respectively for fourteen days. Subsequently, groups B, C, D, and E received single-dose injections of CCl₄ on day fourteen, precisely one hour after their last respective pretreatments.

Results

The in vitro lipoxygenase inhibition by NHEAE increases as the concentration of NHEAE increases compared to standard. The NHEAE pretreatment exhibited protective effects against CCl₄-induced impairments by preventing pathological lesions, linkages of tissue damage biomarker enzymes, and overexpression of NF-kB and TNF-α.

Conclusion

NHEAE demonstrated in vitro lipoxygenase inhibition and in vivo protection against CCl4-induced TNF-α upregulation in female Wistar rats.
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引用次数: 0
Evaluation of hypoglycaemic, hypolipidemic and glucose tolerant effect of Henna leaves on fructose-induced metabolic syndromes in Wistar rats
Pub Date : 2025-01-06 DOI: 10.1016/j.prenap.2025.100150
Youssef S'hih , Ibrahim Hinad , Abdechahid Loukili , Abdelhalem Mesfioui , Moulay Laarbi Ouahidi

Introduction

The presence of fructose in the diet can cause metabolic syndromes (MS), which can lead to serious complications such as type 2 diabetes. Lawsonia inermis (LI) leaves are commonly used as a treatment, but the studies on their hypoglycaemic and hypolipidemic effects on fructose-induced Wistar rats are very limited. The aim of this study was to evaluate the hypoglycaemic and hypolipidemic effect of aqueous extract of Lawsonia inermis leaves (AELIL) in hyperglycaemic and hyperlipidaemic (HH) male Wistar rats induced by a high fructose diet (HFD).

Methods

To induce MS in Wistar rats by HFD, 6 groups (n = 6) were used, 1st and 2nd consisted of normal control (NC) rats, 3th,4th, 5th and 6th where the rats received HFD (20 % then 25 % w/v) (NF) for 12 weeks, followed by measurement of body weight (BW), fasting blood glucose (FBG), oral glucose tolerance test (OGTT), glucose, cholesterol (Chol) and triglyceride (TG) plasma levels. To assess the hypoglycaemic and hypolipidemic effect of AELIL, a dose of 500 mg.kg−1bw was tested by repeated oral administration for 28 days, for which 4 groups of rats were formed, the 1st was used as normal control (NC), the 2nd was HH control (HHC), the 3rd (HTM) and the 4th (HTEL) were HH groups to which the drug and the extract were administered. During treatment, changes in FBG and BW were recorded, oral glucose tolerance test (OGTT), total glucose, Chol and TG plasma levels were measured for all groups at the end of the experiments.

Results

During SM induction, HFD caused a highly significant increase (0.001) in mean of BW (387.25 ± 9.21 vs 283.33 ± 7.00 g), FBG (129.19 ± 3.46 vs 89.33 ± 2.73 mg. dl−1) and serum concentration of Chol (80.67 ± 2.72 vs 53.05 ± 3.84) and TG (151.48 ± 3.46 vs 73.51 ± 2.78) compared with the control, while AELIL showed anti-hyperglycaemic, anti-hyperlipidaemic and tolerance glucose activities with a highly significant (0.001) decrease in serum concentration of glucose (98.78 ± 3.36 mg/dl vs 129.09 ± 2.48 mg/dl), cholesterol (97.55 ± 2.29 mg/dl vs. 104.09 ± 3.43 mg/dl) and TG (94.17 ± 3.94 mg/dl vs. 151.35 ± 3.56 mg/dl) compared with the control, these activities were approximately similar to those of the drug and were accompanied by a significant (p ⩽ 0.05) decrease in the BW of rats' (440.66 ± 8.25 vs. 465.33 ± 3.94687 g) compared with the control at the end of the 4th week of treatment.

Conclusion

HFD for 12 weeks caused significant hyperglycaemia and hyperlipidaemia but did not affect liver, pancreatic, and renal tissues of Wistar rats, whereas repeated treatment for 4 weeks with AELIL showed significant hypoglycaemic, hypolipidemic, and glucose tolerance effects, with different possible mechanisms of action. However, further studies are needed to verify and clarify its effects.
{"title":"Evaluation of hypoglycaemic, hypolipidemic and glucose tolerant effect of Henna leaves on fructose-induced metabolic syndromes in Wistar rats","authors":"Youssef S'hih ,&nbsp;Ibrahim Hinad ,&nbsp;Abdechahid Loukili ,&nbsp;Abdelhalem Mesfioui ,&nbsp;Moulay Laarbi Ouahidi","doi":"10.1016/j.prenap.2025.100150","DOIUrl":"10.1016/j.prenap.2025.100150","url":null,"abstract":"<div><h3>Introduction</h3><div>The presence of fructose in the diet can cause metabolic syndromes (MS), which can lead to serious complications such as type 2 diabetes. Lawsonia inermis (LI) leaves are commonly used as a treatment, but the studies on their hypoglycaemic and hypolipidemic effects on fructose-induced Wistar rats are very limited. The aim of this study was to evaluate the hypoglycaemic and hypolipidemic effect of aqueous extract of Lawsonia inermis leaves (AELIL) in hyperglycaemic and hyperlipidaemic (HH) male Wistar rats induced by a high fructose diet (HFD).</div></div><div><h3>Methods</h3><div>To induce MS in Wistar rats by HFD, 6 groups (n = 6) were used, 1st and 2nd consisted of normal control (NC) rats, 3th,4th, 5th and 6th where the rats received HFD (20 % then 25 % w/v) (NF) for 12 weeks, followed by measurement of body weight (BW), fasting blood glucose (FBG), oral glucose tolerance test (OGTT), glucose, cholesterol (Chol) and triglyceride (TG) plasma levels. To assess the hypoglycaemic and hypolipidemic effect of AELIL, a dose of 500 mg.kg<sup>−1</sup><sub>bw</sub> was tested by repeated oral administration for 28 days, for which 4 groups of rats were formed, the 1st was used as normal control (NC), the 2nd was HH control (HHC), the 3rd (HTM) and the 4th (HTEL) were HH groups to which the drug and the extract were administered. During treatment, changes in FBG and BW were recorded, oral glucose tolerance test (OGTT), total glucose, Chol and TG plasma levels were measured for all groups at the end of the experiments.</div></div><div><h3>Results</h3><div>During SM induction, HFD caused a highly significant increase (0.001) in mean of BW (387.25 ± 9.21 vs 283.33 ± 7.00 g), FBG (129.19 ± 3.46 vs 89.33 ± 2.73 mg. dl<sup>−1</sup>) and serum concentration of Chol (80.67 ± 2.72 vs 53.05 ± 3.84) and TG (151.48 ± 3.46 vs 73.51 ± 2.78) compared with the control, while AELIL showed anti-hyperglycaemic, anti-hyperlipidaemic and tolerance glucose activities with a highly significant (0.001) decrease in serum concentration of glucose (98.78 ± 3.36 mg/dl vs 129.09 ± 2.48 mg/dl), cholesterol (97.55 ± 2.29 mg/dl vs. 104.09 ± 3.43 mg/dl) and TG (94.17 ± 3.94 mg/dl vs. 151.35 ± 3.56 mg/dl) compared with the control, these activities were approximately similar to those of the drug and were accompanied by a significant (p ⩽ 0.05) decrease in the BW of rats' (440.66 ± 8.25 vs. 465.33 ± 3.94687 g) compared with the control at the end of the 4th week of treatment.</div></div><div><h3>Conclusion</h3><div>HFD for 12 weeks caused significant hyperglycaemia and hyperlipidaemia but did not affect liver, pancreatic, and renal tissues of Wistar rats, whereas repeated treatment for 4 weeks with AELIL showed significant hypoglycaemic, hypolipidemic, and glucose tolerance effects, with different possible mechanisms of action. However, further studies are needed to verify and clarify its effects.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"6 ","pages":"Article 100150"},"PeriodicalIF":0.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143156803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
HPLC-HRMS-SPE-NMR analysis of bioactive fractions from Thunbergia laurifolia and Senegalia rugata leaves extracts and the effects on Nrf2, HMOX-1, NQO1, and CYP1A1 expressions
Pub Date : 2025-01-05 DOI: 10.1016/j.prenap.2025.100146
Natchagorn Lumlerdkij , Yong Zhao , Rita de Cássia Lemos Lima , Pravit Akarasereenont , Dan Staerk , Michael Heinrich
Thunbergia laurifolia and Senegalia rugata leaves have been used as cancer prevention in Thai traditional medicine and showed promising chemopreventive effects in vitro in previous studies. However, the relevant mechanism and the active metabolites were still unknown. The objectives of this study are to investigate chemopreventive mechanisms, identify active fractions, and to provide information on their phytochemistry. The effects of the extracts on gene expressions of HepG2 cells were investigated using real-time PCR. High-resolution radical scavenging assay to identify active fractions was performed using ABTS•+ reduction assay. Chemical characterization of the active fractions was then performed by HPLC-HRMS-SPE-NMR analysis. T.laurifolia leaves extract did not act via induction of NQO1, Nrf2, and HMOX-1 gene expressions. Rosmarinic acid could be the active metabolite. Mechanisms of S.rugata leaves extract might be due to the induction of Nrf2 expression. Three apigenin glucosides, including 3,6-di-C-glucosyl apigenin, isoschaftoside, and schaftoside, were reported in S.rugata for the first time and might contribute to the activity. In addition, the effect on CYP1A1 expression suggested that there was a low risk of DNA damage from both leave extracts.
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引用次数: 0
Green synthesis of silver nanoparticles using Boerhavia diffusa plant and the potential of its antioxidant and anticancer efficacy
Pub Date : 2025-01-03 DOI: 10.1016/j.prenap.2025.100142
Jasmin Maria James , Alex Yagoo , Jelin Vilvest , A. Arokia Ahino Jessie
Nanotechnology, which involves manipulating materials at the nanoscale (1–100 nanometers), offers unique properties with broad applications. This study focuses on the green synthesis of silver nanoparticles (AgNPs) using Boerhavia diffusa extract (BD extract), a method that is both cost-effective and environmentally friendly. The synthesized AgNPs were characterized using UV–visible spectroscopy, X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), and energy dispersive X-ray analysis (EDAX). The UV–visible spectroscopy results confirmed the formation of AgNPs with a characteristic peak at 427 nm. XRD analysis revealed a crystalline structure with an average crystallite size of 34 nm. FESEM images showed spherical nanoparticles ranging from 30 to 40 nm, while EDAX confirmed the presence of pure silver. The DPPH radical scavenging assay demonstrated strong antioxidant activity, with the AgNPs achieving 78.57 % scavenging efficiency in a concentration-dependent manner. Cytotoxicity studies on HeLa cells indicated significant anticancer potential, with a 64.12 % inhibition of cell growth at 100 μg/mL and an IC50 value of 45.47 μg/mL. Morphological observations of treated cells revealed apoptosis, marked by cell shrinkage, membrane blebbing, and the formation of apoptotic bodies. These results highlight the potential of BD- mediated AgNPs in both antioxidant and anticancer applications, while also suggesting their use as eco-friendly nanoparticle-based insecticides. The study provides a sustainable approach to nanoparticle synthesis with promising implications for biomedical and agricultural fields.
{"title":"Green synthesis of silver nanoparticles using Boerhavia diffusa plant and the potential of its antioxidant and anticancer efficacy","authors":"Jasmin Maria James ,&nbsp;Alex Yagoo ,&nbsp;Jelin Vilvest ,&nbsp;A. Arokia Ahino Jessie","doi":"10.1016/j.prenap.2025.100142","DOIUrl":"10.1016/j.prenap.2025.100142","url":null,"abstract":"<div><div>Nanotechnology, which involves manipulating materials at the nanoscale (1–100 nanometers), offers unique properties with broad applications. This study focuses on the green synthesis of silver nanoparticles (AgNPs) using <em>Boerhavia diffusa</em> extract (BD extract), a method that is both cost-effective and environmentally friendly. The synthesized AgNPs were characterized using UV–visible spectroscopy, X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), and energy dispersive X-ray analysis (EDAX). The UV–visible spectroscopy results confirmed the formation of AgNPs with a characteristic peak at 427 nm. XRD analysis revealed a crystalline structure with an average crystallite size of 34 nm. FESEM images showed spherical nanoparticles ranging from 30 to 40 nm, while EDAX confirmed the presence of pure silver. The DPPH radical scavenging assay demonstrated strong antioxidant activity, with the AgNPs achieving 78.57 % scavenging efficiency in a concentration-dependent manner. Cytotoxicity studies on HeLa cells indicated significant anticancer potential, with a 64.12 % inhibition of cell growth at 100 μg/mL and an IC50 value of 45.47 μg/mL. Morphological observations of treated cells revealed apoptosis, marked by cell shrinkage, membrane blebbing, and the formation of apoptotic bodies. These results highlight the potential of BD- mediated AgNPs in both antioxidant and anticancer applications, while also suggesting their use as eco-friendly nanoparticle-based insecticides. The study provides a sustainable approach to nanoparticle synthesis with promising implications for biomedical and agricultural fields.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"6 ","pages":"Article 100142"},"PeriodicalIF":0.0,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143156727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Pharmacological Research - Natural Products
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