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Hepato-specific activity of andrographolide, a major constituent of Andrographis paniculata (Burm. f.) Wall. ex Nees for targeting liver diseases
Pub Date : 2025-01-31 DOI: 10.1016/j.prenap.2025.100155
Kallol Roy , Pankaj Barman , Saikat Haldar , Jatin Kalita , Rituraj Konwar

Background

Liver diseases accounts for considerable morbidity and mortality worldwide and current standard therapies often suffer from various challenges including inadequate efficacy and detrimental side effects. Andrographis paniculata (Burm. f.) Wall. ex Nees is a seasonal plant endemic to Southeast Asia employed traditionally during in injury, respiratory infections, fever, headache, liver, and other gastrointestinal disorders. Andrographolide, a key active molecule of the plant exhibits broad range of pharmacological activities against various diseases.

Purpose

The aim of the review is to present all scientific evidences of traditional uses of A. paniculata and its important phytochemical constituent andrographolide on major liver diseases and other liver complications.

Materials and methods

We have collected the previous scientific reports by searching common databases like “Pubmed”, “Google scholar”, “Science direct”, “Research Gate” with primary search common keywords “andrographolide”, “Andrographis paniculata”, “traditional”, “Ethno* ”, “medicine”, “Liver” “Hepat* ” “Diseases” etc. to retrieve maximum possible literature reports. The initially collected reports were further screened for their inclusion based on peer-review status or other authenticity confirmable status of the report and actual relevance. In addition, books, thesis, reports retrieved through Google search engine from other open access sources were also included for further screening and inclusion.

Results

The medicinal plant A. paniculata used traditionally since time immemorial for various purposes including liver disorders. Andrographolide is generally tolerable and possibly does not induce significant toxicity. Andrographolide played important role in different pharmacodynamic process such as in oxidative disbalance, lipid peroxidation, inflammation, and disruption of immune response, which are involved in the initiation of liver diseases. It targets various signaling pathways including TRL4/NFKB and TGFβ1/smad2, and p38 MAPK/Nrf2/HO-1 to ameliorate liver diseases. Clinical investigations of A. paniculata and andrographolide alone or in combined form have showed significant potential for their use in liver diseases.

Conclusions

Based on all the reported effects of A. paniculata plant gained through traditional clinical studies along with specific pharmacological efficacy of its constituent andrographolide, it can be viewed that there is a considerable potential of this plant for development of new preventive and therapeutic applications against hepatic diseases.
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引用次数: 0
Anti-cancer potential of hydroethanolic extracts of Kyllinga nemoralis: An in vitro and in-silico studies
Pub Date : 2025-01-31 DOI: 10.1016/j.prenap.2025.100161
Eunice E. Ampem Danso , Justice Kumi , Abigail Aning , Sherif Hamidu , Janet Ampofo , Latif Adams , Isaac Asiamah , Francis Ackah Armah , Alexander K. Nyarko , Desmond Omane Acheampong

Introduction

This study aims to investigate the antioxidant and anti-proliferative properties of Kalinga nemoralis to regulate the production and application of herbal preparations.

Method

The leaves, roots and the whole plant extracts of Kyllinga nemoralis (KNL, KNR and KNW) were evaluated for antioxidant capacity, flavonoid content (TFC), phenolic content (TPC), in vitro cytotoxicity using Folin-Ciocalteu, Aluminium Chloride colorimetric methods and DPPH (2, 2-diphenyl-1-picrylhydrazyl) and FRAP assays respectively. LC-MS chemical profile was obtained by Agilent HPLC system.
The results obtained showed that, KNL extracts shown the highest TFC (16421.33 ± 0.06 mg QE/g) followed by KNW (10531 ± 0.02 mg QE/g) and KNR extracts (4741 ± 0.04 mg QE/g) with TFC/TPC ratio of 65.03, 58.50 and 23.75 respectively. The EC50 values of both DPPH and FRAP assays for the extracts ranged from 0.033 ± 0.07–4.10 ± 0.67 mg/mL. KNL and KNR had the strongest ferric reducing activity (EC50 values of 0.88 ± 0.20 mg/mL and 1.52 ± 0.36 mg/mL) while KNW had the least DPPH radical scavenging activity (2.48 ± 0.35 µg/mL). The IC50 value for each extract was greater than 1000 µg/mL, indicating minimal cytotoxicity against PNT2 cell line. KNR and KNW exhibited the strongest inhibitory activity against the PC3 cell line with an IC50 values of 52.65 ± 1.11 and 53.20 ± 0.80 µg/mL respectively. KNL exhibited a good inhibitory activity against the cancer cell line with an IC50 value of 68.54 ± 9.99. The selectivity indices of extracts were greater than 2. LC-MS profile showed four primary peaks representing combined plant constituents, with 12 recognized compounds and five undetermined compounds.

Conclusion

Kyllinga nemoralis demonstrates antioxidant activity and antiproliferative effects against PC3 cell lines, attributed to its bioactive compounds. Among these, Flufenacet, Diazoxide, and N-(2-Hydroxyphenyl)piperazine exhibited the highest drug-likeness scores with significant bioactivity.
{"title":"Anti-cancer potential of hydroethanolic extracts of Kyllinga nemoralis: An in vitro and in-silico studies","authors":"Eunice E. Ampem Danso ,&nbsp;Justice Kumi ,&nbsp;Abigail Aning ,&nbsp;Sherif Hamidu ,&nbsp;Janet Ampofo ,&nbsp;Latif Adams ,&nbsp;Isaac Asiamah ,&nbsp;Francis Ackah Armah ,&nbsp;Alexander K. Nyarko ,&nbsp;Desmond Omane Acheampong","doi":"10.1016/j.prenap.2025.100161","DOIUrl":"10.1016/j.prenap.2025.100161","url":null,"abstract":"<div><h3>Introduction</h3><div>This study aims to investigate the antioxidant and anti-proliferative properties of <em>Kalinga nemoralis</em> to regulate the production and application of herbal preparations.</div></div><div><h3>Method</h3><div>The leaves, roots and the whole plant extracts of <em>Kyllinga nemoralis</em> (KNL, KNR and KNW) were evaluated for antioxidant capacity, flavonoid content (TFC), phenolic content (TPC), in vitro cytotoxicity using Folin-Ciocalteu, Aluminium Chloride colorimetric methods and DPPH (2, 2-diphenyl-1-picrylhydrazyl) and FRAP assays respectively. LC-MS chemical profile was obtained by Agilent HPLC system.</div><div>The results obtained showed that, KNL extracts shown the highest TFC (16421.33 ± 0.06 mg QE/g) followed by KNW (10531 ± 0.02 mg QE/g) and KNR extracts (4741 ± 0.04 mg QE/g) with TFC/TPC ratio of 65.03, 58.50 and 23.75 respectively. The EC<sub>50</sub> values of both DPPH and FRAP assays for the extracts ranged from 0.033 ± 0.07–4.10 ± 0.67 mg/mL. KNL and KNR had the strongest ferric reducing activity (EC<sub>50</sub> values of 0.88 ± 0.20 mg/mL and 1.52 ± 0.36 mg/mL) while KNW had the least DPPH radical scavenging activity (2.48 ± 0.35 µg/mL). The IC<sub>50</sub> value for each extract was greater than 1000 µg/mL, indicating minimal cytotoxicity against PNT2 cell line. KNR and KNW exhibited the strongest inhibitory activity against the PC3 cell line with an IC<sub>50</sub> values of 52.65 ± 1.11 and 53.20 ± 0.80 µg/mL respectively. KNL exhibited a good inhibitory activity against the cancer cell line with an IC<sub>50</sub> value of 68.54 ± 9.99. The selectivity indices of extracts were greater than 2. LC-MS profile showed four primary peaks representing combined plant constituents, with 12 recognized compounds and five undetermined compounds.</div></div><div><h3>Conclusion</h3><div><em>Kyllinga nemoralis</em> demonstrates antioxidant activity and antiproliferative effects against PC3 cell lines, attributed to its bioactive compounds. Among these, Flufenacet, Diazoxide, and N-(2-Hydroxyphenyl)piperazine exhibited the highest drug-likeness scores with significant bioactivity.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"6 ","pages":"Article 100161"},"PeriodicalIF":0.0,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143156375","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
Bergenia ciliata, a Himalayan medicinal herb with Chinese ethnobotanical roots, alleviates L-arginine-induced acute pancreatitis through modulation of inflammation and oxidative stress: Insights from in Silico and in Vivo studies
Pub Date : 2025-01-29 DOI: 10.1016/j.prenap.2025.100164
Tridip Jyoti Das , Shaurya Tiwari , Anjini Bellai , Upasa Gowala , Hui Tag , Kunal Bhattacharya , Pallabi Kalita Hui
Acute pancreatitis (AP) is an inflammatory disorder of the exocrine pancreas, where oxidative stress and inflammatory cytokines play a key role in the induction and progression of the disease. The present study aims to examine the in-vivo effect of methanol extract of Bergenia ciliata rhizome (MEBCR) on L-arginine induced AP in mice and to identify novel drug candidates as alternative therapeutic options in the management of acute pancreatitis. Various markers for pancreatic function, inflammation, oxidative stress, and histological parameter were assessed. Our results indicate that mice treated with MEBCR was able to control the L-arginine-induced changes in pancreatic enzymes, oxidative stress markers (MDA, GSH and nitrite), pancreatic inflammatory markers (MPO, IL-1β, TNF-α and IL-6) as well as histological changes in the pancreatic and liver tissues. MEBCR dose dependently decreases the pro-inflammatory cytokines levels such as TNF-α, IL-6, and IL-1β. MEBCR improved the antioxidant defence by improving Nrf-2 and SOD-1 expression. When considered collectively, our findings indicate that MEBCR pretreatment inhibits AP. These outcomes may be related to the antioxidant activity of the antioxidant enzyme, which was brought about by the Nrf2/ARE signaling pathway being activated. Thus, up-regulating the expression of antioxidant enzymes and activating the endogenous antioxidant pathway Nrf2/ARE may represent viable treatment targets for MEBCR during AP. In our in silico analysis, chelidonine demonstrated favourable pharmacological properties and a notable binding affinity of −11.0 kcal/mol towards the Keap1 protein, and the chelidonine-Keap1 complex remained stable through 100 ns simulation with GROMACS without undergoing major fluctuations.
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引用次数: 0
Acute toxicity and antidiabetic potential of moroccan Lavandula mairei essential oil in induced type 1 and type 2 diabetes
Pub Date : 2025-01-29 DOI: 10.1016/j.prenap.2025.100162
Fatima Ez-zahra Ousaid , Fouzia Hmimid , Fatima Abdou-Allah , Lamiaa Ait Si , Meryem Souidek , Fatima Azzahra Lahlou , Imane Nait Irahal , Ismail Guenaou , Chaimae Hilali , Mehdi Karkouri , Mostafa Kabine , Noureddine Bourhim
Lavandula mairei (L. mairei) is a species of plant from the Lamiaceae family that is endemic to Morocco and known for its aromatic and medicinal properties. The aim of the study was to evaluate toxicity and antidiabetic properties of L. mairei essential oil (EO). The toxicity study was conducted on mice by administration of a single oral dose, followed by observation for 14 days. Clinical signs and symptoms associated with each dose administered were closely monitored. Serum biochemical analyses of various biomarkers of hepatic and renal functions, lipid profile, as well as histological sections were examined. Moreover, the antidiabetic activity was evaluated in vivo in type 1 diabetic rats and, in vitro assays were carried out using enzyme suspensions prepared from the liver of type 2 diabetic rats. Additionally, we assessed the ability of the EO to inhibit the enzymatic activity of polyol pathway, α -amylase and α -glucosidase. The biochemical results indicated that the EO was unsafe at a dose of 1000 mg/kg body weight, while histological sections showed clear signs of hepatotoxicity and nephrotoxicity at both 1000 mg/kg and 500 mg/kg. The EO showed a significant antidiabetic potential with a decrease in glycaemia and significant inhibitory effects on some metabolic enzymes. L. mairei EO may be a promising natural remedy for the management of diabetes, but rigorous scientific studies are needed to validate its efficacy and safety.
{"title":"Acute toxicity and antidiabetic potential of moroccan Lavandula mairei essential oil in induced type 1 and type 2 diabetes","authors":"Fatima Ez-zahra Ousaid ,&nbsp;Fouzia Hmimid ,&nbsp;Fatima Abdou-Allah ,&nbsp;Lamiaa Ait Si ,&nbsp;Meryem Souidek ,&nbsp;Fatima Azzahra Lahlou ,&nbsp;Imane Nait Irahal ,&nbsp;Ismail Guenaou ,&nbsp;Chaimae Hilali ,&nbsp;Mehdi Karkouri ,&nbsp;Mostafa Kabine ,&nbsp;Noureddine Bourhim","doi":"10.1016/j.prenap.2025.100162","DOIUrl":"10.1016/j.prenap.2025.100162","url":null,"abstract":"<div><div><em>Lavandula mairei</em> (<em>L. mairei</em>) is a species of plant from the <em>Lamiaceae</em> family that is endemic to Morocco and known for its aromatic and medicinal properties. The aim of the study was to evaluate toxicity and antidiabetic properties of <em>L. mairei</em> essential oil (EO). The toxicity study was conducted on mice by administration of a single oral dose, followed by observation for 14 days. Clinical signs and symptoms associated with each dose administered were closely monitored. Serum biochemical analyses of various biomarkers of hepatic and renal functions, lipid profile, as well as histological sections were examined. Moreover, the antidiabetic activity was evaluated <em>in vivo</em> in type 1 diabetic rats and, <em>in vitro</em> assays were carried out using enzyme suspensions prepared from the liver of type 2 diabetic rats. Additionally, we assessed the ability of the EO to inhibit the enzymatic activity of polyol pathway, α -amylase and α -glucosidase. The biochemical results indicated that the EO was unsafe at a dose of 1000 mg/kg body weight, while histological sections showed clear signs of hepatotoxicity and nephrotoxicity at both 1000 mg/kg and 500 mg/kg. The EO showed a significant antidiabetic potential with a decrease in glycaemia and significant inhibitory effects on some metabolic enzymes. <em>L. mairei</em> EO may be a promising natural remedy for the management of diabetes, but rigorous scientific studies are needed to validate its efficacy and safety.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"6 ","pages":"Article 100162"},"PeriodicalIF":0.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143156371","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
Antimicrobial activity of selected native Australian Terminalia spp. against gastrointestinal pathogens and potentiation of selected antibiotics
Pub Date : 2025-01-28 DOI: 10.1016/j.prenap.2025.100158
Muhammad Jawad Yousaf Zai , Matthew James Cheesman , Ian Edwin Cock
Terminalia species (Family: Combretaceae) have a wide variety of traditional therapeutic, including to treat bacterial infections. However, no previous studies have verified the antibacterial activity of Terminalia petiolaris A. Cunn. Ex Benth. or Terminalia grandiflora Benth. against gastrointestinal pathogens. Similarly, Terminalia ferdinandiana extracts have not yet been evaluated against many gastrointestinal bacteria. Herein, we quantify the minimum inhibitory concentrations (MIC) of T. ferdinandiana leaf and fruit extracts, as well as T. petiolaris and T. grandiflora leaf extracts against several bacterial gastrointestinal pathogens. Aqueous and methanolic T. ferdinandiana leaf extracts exhibited noteworthy inhibitory activity against multiple bacteria, whilst the corresponding fruit extracts displayed good activity against multiple Gram-negative pathogens, but were completely ineffective against B. cereus. The methanolic T. petiolaris extract showed low activity against all pathogens except S. flexneri, against which the activity was moderate. The methanolic T. grandiflora extract was ineffective against all of the bacteria tested. In contrast, all ethyl acetate extracts were effective inhibitors of bacterial growth, except the T. ferdinandiana leaf extract, which potently inhibited A. faecalis growth (MIC = 75 µg/mL). Combining the plant extracts with selected conventional antibiotics substantially enhanced the antibacterial activity of the mixture. Two synergistic combinations, as well as thirty-six additive, fifty-six indifferent, and twenty-four antagonistic combinations were identified. The safety of the extracts was evaluated by screening for toxicity towards human dermal fibroblast cells, with all extracts were classified as non-toxic. The growth inhibitory mechanism(s) of the extracts are discussed, with reference to their phytochemical composition.
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引用次数: 0
Anti-nociceptive activity of Biochanin A- an important isoflavone from natural source
Pub Date : 2025-01-28 DOI: 10.1016/j.prenap.2025.100157
Shreya R. Savla , Manisha J. Oza , Ankit P. Laddha , Yogesh A. Kulkarni

Introduction

Biochanin A is an important isoflavone reported in plants such as Trifolium pratense. It has exhibited significant anti-inflammatory activity. The present work was designed to study its effects in animal models of nociception.

Methods

Albino Wistar rats were orally administered with Biochanin A, at dose levels of 10, 20, and 40 mg/kg. The anti-nociceptive activity was evaluated using hot plate, tail-immersion, and formalin-induced nociception models.

Results

In tail immersion test, maximum tail withdrawal response of animals treated with Biochanin A was observed at dose of 40 mg/kg at 3 h (p < 0.001), which was significantly higher than control animals. In the hot plate test, Biochanin A treated rats showed significant improvement in response time, achieving a peak response at 45 min (p < 0.001) when compared to control animals. Treatment with Biochanin A also showed a significantly decreased nociception in the formalin test (p < 0.001) at doses of 20 and 40 mg/kg.

Conclusion

From the results, it can be concluded that Biochanin A has significant effect in management of central and peripheral pain.
{"title":"Anti-nociceptive activity of Biochanin A- an important isoflavone from natural source","authors":"Shreya R. Savla ,&nbsp;Manisha J. Oza ,&nbsp;Ankit P. Laddha ,&nbsp;Yogesh A. Kulkarni","doi":"10.1016/j.prenap.2025.100157","DOIUrl":"10.1016/j.prenap.2025.100157","url":null,"abstract":"<div><h3>Introduction</h3><div>Biochanin A is an important isoflavone reported in plants such as <em>Trifolium pratense</em>. It has exhibited significant anti-inflammatory activity. The present work was designed to study its effects in animal models of nociception.</div></div><div><h3>Methods</h3><div>Albino <em>Wistar</em> rats were orally administered with Biochanin A, at dose levels of 10, 20, and 40 mg/kg. The anti-nociceptive activity was evaluated using hot plate, tail-immersion, and formalin-induced nociception models.</div></div><div><h3>Results</h3><div>In tail immersion test, maximum tail withdrawal response of animals treated with Biochanin A was observed at dose of 40 mg/kg at 3 h (p &lt; 0.001), which was significantly higher than control animals. In the hot plate test, Biochanin A treated rats showed significant improvement in response time, achieving a peak response at 45 min (p &lt; 0.001) when compared to control animals. Treatment with Biochanin A also showed a significantly decreased nociception in the formalin test (p &lt; 0.001) at doses of 20 and 40 mg/kg.</div></div><div><h3>Conclusion</h3><div>From the results, it can be concluded that Biochanin A has significant effect in management of central and peripheral pain.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"6 ","pages":"Article 100157"},"PeriodicalIF":0.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143201851","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
AYUSH-64 modulates Th17/Treg balance to attenuate LPS-induced inflammation in cell-based assays and BALB/c mice model
Pub Date : 2025-01-28 DOI: 10.1016/j.prenap.2025.100159
M.R. Kamala Priya , Pallerla Naveen Reddy , Yamini Goswami , Anamika Dwivedi , Mukta Pujani , Madhu Dikshit , Ruchi Tandon
AYUSH-64, a polyherbal formulation, has demonstrated therapeutic utility in managing several inflammatory diseases over the past three decades. Notably, during the COVID-19 pandemic, randomized clinical trials highlighted its efficacy in treating mild to moderate disease. Strong immunity is crucial for maintaining health and providing robust protection against infections and diseases. This study aimed to adopt an evidence-based approach to evaluate the anti-inflammatory and immunomodulatory potential of AYUSH-64 through various pharmacological models. Several in vitro cell-based assays were employed to assess the effects of AYUSH-64, using lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells (PBMCs), differentiated THP-1 cells, and A549 adenocarcinoma cell lines. Additionally, LPS-induced lung inflammation in a BALB/c mouse model was used to evaluate its anti-inflammatory potential in vivo. The in vitro experiments revealed that LPS stimulation (1 µg/ml) significantly increased the expression of pro-inflammatory cytokines, including TNF-α, IL-6, and IL-8, in PBMCs, differentiated THP-1 cells, and A549 cells. AYUSH-64, at concentrations of 10 mg/ml, 3 mg/ml, and 1 mg/ml, reduced the expression of these cytokines in a dose-dependent manner. Furthermore, AYUSH-64 suppressed LPS-induced IL-17 levels in PBMCs, while enhancing the regulatory T cell (Treg) population and FoxP3 expression, suggesting a modulatory effect on immune response. In the in vivo model, AYUSH-64 at 100 mg/kg and 30 mg/kg significantly reduced neutrophil infiltration in BALB/c mice challenged intranasally with LPS (25 µg in 200 µL PBS per mouse). This was accompanied by improved lung pathophysiology and reduced pro-inflammatory cytokine levels in lung tissues. These findings underscore the distinct anti-inflammatory effects of AYUSH-64 across all studied models. Moreover, treatment with AYUSH-64 resulted in an increased Treg population and elevated FoxP3 levels in PBMCs, indicating its immunoregulatory potential. In conclusion, AYUSH-64 demonstrates promise as a herbal therapeutic for managing inflammation and enhancing immunity, warranting further investigation for its potential applications in human health.
{"title":"AYUSH-64 modulates Th17/Treg balance to attenuate LPS-induced inflammation in cell-based assays and BALB/c mice model","authors":"M.R. Kamala Priya ,&nbsp;Pallerla Naveen Reddy ,&nbsp;Yamini Goswami ,&nbsp;Anamika Dwivedi ,&nbsp;Mukta Pujani ,&nbsp;Madhu Dikshit ,&nbsp;Ruchi Tandon","doi":"10.1016/j.prenap.2025.100159","DOIUrl":"10.1016/j.prenap.2025.100159","url":null,"abstract":"<div><div>AYUSH-64, a polyherbal formulation, has demonstrated therapeutic utility in managing several inflammatory diseases over the past three decades. Notably, during the COVID-19 pandemic, randomized clinical trials highlighted its efficacy in treating mild to moderate disease. Strong immunity is crucial for maintaining health and providing robust protection against infections and diseases. This study aimed to adopt an evidence-based approach to evaluate the anti-inflammatory and immunomodulatory potential of AYUSH-64 through various pharmacological models. Several <em>in vitro</em> cell-based assays were employed to assess the effects of AYUSH-64, using lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells (PBMCs), differentiated THP-1 cells, and A549 adenocarcinoma cell lines. Additionally, LPS-induced lung inflammation in a BALB/c mouse model was used to evaluate its anti-inflammatory potential <em>in vivo</em>. The <em>in vitro</em> experiments revealed that LPS stimulation (1 µg/ml) significantly increased the expression of pro-inflammatory cytokines, including TNF-α, IL-6, and IL-8, in PBMCs, differentiated THP-1 cells, and A549 cells. AYUSH-64, at concentrations of 10 mg/ml, 3 mg/ml, and 1 mg/ml, reduced the expression of these cytokines in a dose-dependent manner. Furthermore, AYUSH-64 suppressed LPS-induced IL-17 levels in PBMCs, while enhancing the regulatory T cell (Treg) population and FoxP3 expression, suggesting a modulatory effect on immune response. In the <em>in vivo</em> model, AYUSH-64 at 100 mg/kg and 30 mg/kg significantly reduced neutrophil infiltration in BALB/c mice challenged intranasally with LPS (25 µg in 200 µL PBS per mouse). This was accompanied by improved lung pathophysiology and reduced pro-inflammatory cytokine levels in lung tissues. These findings underscore the distinct anti-inflammatory effects of AYUSH-64 across all studied models. Moreover, treatment with AYUSH-64 resulted in an increased Treg population and elevated FoxP3 levels in PBMCs, indicating its immunoregulatory potential. In conclusion, AYUSH-64 demonstrates promise as a herbal therapeutic for managing inflammation and enhancing immunity, warranting further investigation for its potential applications in human health.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"6 ","pages":"Article 100159"},"PeriodicalIF":0.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143156372","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
Exploring synergistic potential of phytomolecules-antibiotics combination against Escherichia coli: An integrated approach using structure based drug design
Pub Date : 2025-01-28 DOI: 10.1016/j.prenap.2025.100160
Firuj Ahmed , Hitesh K. Sharma , Monalisa Mukherjee , Pallavi Agarwal , Anoop Kumar , Deepti Pandita , Viney Lather
The rise of antibiotic-resistant Escherichia coli (E. coli), a pathogen responsible for conditions like urinary tract infections, sepsis, and gastroenteritis, presents a critical challenge to public health, necessitating innovative therapeutic strategies. This study investigates the potential of phytomolecules as adjuncts to conventional antibiotics in combating E. coli resistance. Natural compounds, despite their critical role in drug discovery, often lack sufficient potency against resistant bacteria when used alone. However, in combination with antibiotics, they can create a synergistic effect, enhancing antibacterial efficacy and mitigating the risk of further resistance. Our research involved virtual screening of diverse small molecules against key E. coli targets, including PBP2, PBP3, Topoisomerase IV subunits A and B, Extended Spectrum β-lactamase, MurA, and DHFR. Phytomolecules such as thymol, eugenol, xanthohumol, brazilin, quercetin, curcumin, and berberine were identified as promising candidates based on their docking scores, binding free energy, and interactions. These were further assessed for ADMET and drug-likeness properties using pkCSM, SwissADME, and QikProp tools. In vitro testing against E. coli revealed xanthohumol as particularly potent, with a minimum inhibitory concentration (MIC) of 7.8 μg/ml. Other molecules, including berberine, citral, thymol, and curcumin, showed MICs ranging from 62.5 to 250 μg/ml, while quercetin and eugenol had MICs between 500 and 1000 μg/ml. Notably, xanthohumol exhibited strong synergy with ampicillin, underscoring its significant antibacterial potential. These results suggest that phytomolecule-antibiotic combinations could serve as a novel approach to enhance the efficacy of existing antibiotics, providing a promising solution to the growing challenge of E. coli antibiotic resistance.
{"title":"Exploring synergistic potential of phytomolecules-antibiotics combination against Escherichia coli: An integrated approach using structure based drug design","authors":"Firuj Ahmed ,&nbsp;Hitesh K. Sharma ,&nbsp;Monalisa Mukherjee ,&nbsp;Pallavi Agarwal ,&nbsp;Anoop Kumar ,&nbsp;Deepti Pandita ,&nbsp;Viney Lather","doi":"10.1016/j.prenap.2025.100160","DOIUrl":"10.1016/j.prenap.2025.100160","url":null,"abstract":"<div><div>The rise of antibiotic-resistant <em>Escherichia coli (E. coli)</em>, a pathogen responsible for conditions like urinary tract infections, sepsis, and gastroenteritis, presents a critical challenge to public health, necessitating innovative therapeutic strategies. This study investigates the potential of phytomolecules as adjuncts to conventional antibiotics in combating <em>E. coli</em> resistance. Natural compounds, despite their critical role in drug discovery, often lack sufficient potency against resistant bacteria when used alone. However, in combination with antibiotics, they can create a synergistic effect, enhancing antibacterial efficacy and mitigating the risk of further resistance. Our research involved virtual screening of diverse small molecules against key <em>E. coli</em> targets, including PBP2, PBP3, Topoisomerase IV subunits A and B, Extended Spectrum β-lactamase, MurA, and DHFR. Phytomolecules such as thymol, eugenol, xanthohumol, brazilin, quercetin, curcumin, and berberine were identified as promising candidates based on their docking scores, binding free energy, and interactions. These were further assessed for ADMET and drug-likeness properties using pkCSM, SwissADME, and QikProp tools. <em>In vitro</em> testing against <em>E. coli</em> revealed xanthohumol as particularly potent, with a minimum inhibitory concentration (MIC) of 7.8 μg/ml. Other molecules, including berberine, citral, thymol, and curcumin, showed MICs ranging from 62.5 to 250 μg/ml, while quercetin and eugenol had MICs between 500 and 1000 μg/ml. Notably, xanthohumol exhibited strong synergy with ampicillin, underscoring its significant antibacterial potential. These results suggest that phytomolecule-antibiotic combinations could serve as a novel approach to enhance the efficacy of existing antibiotics, providing a promising solution to the growing challenge of <em>E. coli</em> antibiotic resistance.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"6 ","pages":"Article 100160"},"PeriodicalIF":0.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143156343","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 antimycobacterial potential, acute toxicity and GC-MS analysis of Berlinia grandiflora (Vahl) Hutch. & Dalziel and Senna occidentalis (L.) link leaves extracts
Pub Date : 2025-01-21 DOI: 10.1016/j.prenap.2025.100154
Kazeem T. Olatunji , Peters O. Oladosu , Matthew O. Kolawole
Senna occidentalis and Berlinia grandiflora are medicinal plants used traditionally in managing infections of pneumonia, cough, tuberculosis, malaria, typhoid, asthma, gastrointestinal disorders, gonorrhea, hemorrhoids liver problems, labour pain during childbirth and as a purgative. This study aimed to determine the antituberculosis activity, acute oral toxicity, and Gas chromatography-mass spectrometry (GC-MS) analysis of the leaves extracts of these plants. 70 % hydro-ethanol extracts and fractions of these plants were tested for antituberculosis activity against clinical Mycobacterium tuberculosis isolate, Mycobacterium bovis (ATCC 27290), and Mycobacterium Smegmatis (ATCC 607). The standard checkerboard assay was utilized to investigate the synergistic effect of the most active fractions. Acute oral toxicity of the most active fractions were studied in mice. The bioactive components in the most active fractions were determined using GC-MS. S. occidentalis extract showed the lowest MIC (391 μg/mL) and MBC (781 μg/mL) against M. tuberculosis significantly at p < 0.05. The hexane fraction of S. occidentalis also showed the lowest MIC (156 μg/mL) and MBC (313 μg/mL) against M. tuberculosis significantly at p < 0.05. The combinatorial study of the n-hexane fractions of these plants against M. tuberculosis, M. bovis and M. smegmatis revealed a synergistic action of ΣFIC= 0.19, ΣFIC= 0.26, and ΣFIC= 0.38 respectively. The acute oral toxicity testing of the n-hexane fractions of these plants revealed no signs of toxicity throughout the observation period. GC-MS analysis of the n-hexane fraction of B. grandiflora revealed 40 components while the n-hexane fraction of S. occidentalis revealed 18 components. The synergistic effect of these two plants can serve as lead in drug development for the treatment of tuberculosis.
{"title":"In vitro antimycobacterial potential, acute toxicity and GC-MS analysis of Berlinia grandiflora (Vahl) Hutch. & Dalziel and Senna occidentalis (L.) link leaves extracts","authors":"Kazeem T. Olatunji ,&nbsp;Peters O. Oladosu ,&nbsp;Matthew O. Kolawole","doi":"10.1016/j.prenap.2025.100154","DOIUrl":"10.1016/j.prenap.2025.100154","url":null,"abstract":"<div><div><em>Senna occidentalis</em> and <em>Berlinia grandiflora</em> are medicinal plants used traditionally in managing infections of pneumonia, cough, tuberculosis, malaria, typhoid, asthma, gastrointestinal disorders, gonorrhea, hemorrhoids liver problems, labour pain during childbirth and as a purgative. This study aimed to determine the antituberculosis activity, acute oral toxicity, and Gas chromatography-mass spectrometry (GC-MS) analysis of the leaves extracts of these plants. 70 % hydro-ethanol extracts and fractions of these plants were tested for antituberculosis activity against clinical <em>Mycobacterium tuberculosis</em> isolate, <em>Mycobacterium bovis</em> (ATCC 27290), and <em>Mycobacterium Smegmatis</em> (ATCC 607)<em>.</em> The standard checkerboard assay was utilized to investigate the synergistic effect of the most active fractions. Acute oral toxicity of the most active fractions were studied in mice. The bioactive components in the most active fractions were determined using GC-MS. <em>S. occidentalis</em> extract showed the lowest MIC (391 μg/mL) and MBC (781 μg/mL) against <em>M. tuberculosis</em> significantly at p &lt; 0.05. The hexane fraction of <em>S. occidentalis</em> also showed the lowest MIC (156 μg/mL) and MBC (313 μg/mL) against <em>M. tuberculosis</em> significantly at p &lt; 0.05. The combinatorial study of the n-hexane fractions of these plants against <em>M. tuberculosis</em>, <em>M. bovis</em> and <em>M. smegmatis</em> revealed a synergistic action of ΣFIC= 0.19, ΣFIC= 0.26, and ΣFIC= 0.38 respectively. The acute oral toxicity testing of the n-hexane fractions of these plants revealed no signs of toxicity throughout the observation period. GC-MS analysis of the n-hexane fraction of <em>B. grandiflora</em> revealed 40 components while the n-hexane fraction of <em>S. occidentalis</em> revealed 18 components. The synergistic effect of these two plants can serve as lead in drug development for the treatment of tuberculosis.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"6 ","pages":"Article 100154"},"PeriodicalIF":0.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143156844","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
Natural remedies for hypertension: A systematic review
Pub Date : 2025-01-11 DOI: 10.1016/j.prenap.2025.100145
Hussam Abdeljabar Ahmad Mizher, Muhammad Iqbal Hamidullah Mohd Noor, Syahrir Zaini
Hypertension is a chronic condition contributing significantly to global morbidity and mortality. Increasingly, natural remedies are being considered for hypertension management due to their accessibility, lower cost, and fewer perceived side effects compared to conventional medications. This systematic review aimed to evaluate the scientific evidence on the effectiveness and safety of various natural remedies for treating hypertension. The review included remedies such as garlic, celery, hibiscus, hawthorn, and herbal formulations used in Traditional Chinese Medicine, among others. Following the PRISMA guidelines, eligible studies were selected from databases such as Cochrane Library and PubMed, with quality assessed using the SIGN methodology checklist. Eighteen studies were included, totalling 1915 participants. While many studies showed that these remedies effectively reduced blood pressure, no study demonstrated superior effectiveness of natural remedies over conventional antihypertensive medications. Safety profiles were generally favourable, with few minor side effects reported. However, due to limited and variable safety data, further independent, high-quality research is needed to comprehensively evaluate the long-term safety and efficacy of these remedies for hypertension management.
{"title":"Natural remedies for hypertension: A systematic review","authors":"Hussam Abdeljabar Ahmad Mizher,&nbsp;Muhammad Iqbal Hamidullah Mohd Noor,&nbsp;Syahrir Zaini","doi":"10.1016/j.prenap.2025.100145","DOIUrl":"10.1016/j.prenap.2025.100145","url":null,"abstract":"<div><div>Hypertension is a chronic condition contributing significantly to global morbidity and mortality. Increasingly, natural remedies are being considered for hypertension management due to their accessibility, lower cost, and fewer perceived side effects compared to conventional medications. This systematic review aimed to evaluate the scientific evidence on the effectiveness and safety of various natural remedies for treating hypertension. The review included remedies such as garlic, celery, hibiscus, hawthorn, and herbal formulations used in Traditional Chinese Medicine, among others. Following the PRISMA guidelines, eligible studies were selected from databases such as Cochrane Library and PubMed, with quality assessed using the SIGN methodology checklist. Eighteen studies were included, totalling 1915 participants. While many studies showed that these remedies effectively reduced blood pressure, no study demonstrated superior effectiveness of natural remedies over conventional antihypertensive medications. Safety profiles were generally favourable, with few minor side effects reported. However, due to limited and variable safety data, further independent, high-quality research is needed to comprehensively evaluate the long-term safety and efficacy of these remedies for hypertension management.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"6 ","pages":"Article 100145"},"PeriodicalIF":0.0,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143156840","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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