cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.30627898.v2
title: Potential pharmacological quality control markers in the traditional Japanese medicine Hangeshashinto: identifying anti-inflammatory ingredients through a cell-based bioassay and multicomponent analysis

description: The traditional Japanese medicine Hangeshashinto (HST) is a multicompound drug used for stomatitis. The identification of HST’s active ingredients is essential for understanding its mechanism of action and establishing pharmacological quality control markers, but remains unclear due to its multicomponent drug. To systematically explore anti-inflammatory ingredients in HST using a combined approach involving a cell-based bioassay and multicomponent analysis, and to identify potential quality marker compounds. A cell-based bioassay modeling stomatitis was established using human oral keratinocytes (HOK), with interleukin (IL)-1β–induced prostaglandin E2 (PGE2) as an inflammatory indicator. The PGE2 inhibitory effects of quality-controlled 101 HST manufacturing lots were compared. Multicomponent analysis was performed on the 101 HST samples, correlating the intensity of 121 component peaks with the pharmacological activities. Ingredients with the highest correlation coefficients were validated for their PGE2 inhibitory effects. A total of 101 HST samples (30 µg/mL: approximately IC<sub>50</sub>) showed consistent inhibition of IL-1β–induced PGE2 production in HOK (41.33%–67.38% with 100% as IL-1β). Correlation analysis between PGE2 inhibitory activities and peak intensity of 121 components revealed the contribution of each ingredient to the pharmacological effect. Eight ingredients (glycycoumarin, neoglycyrol, [6]-shogaol, [8]-shogaol, [10]-shogaol, [6]-gingerol, [8]-gingerol, and [10]-gingerol) with the highest correlation coefficients (below −0.30) exhibited PGE2-inhibitory potential. The standardization of current quality control markers contributes to the stability of HST’s anti-inflammatory effects. The eight components discovered by this integrated analysis method may become novel quality control marker ingredients for further improving the pharmacological quality of HST.
DOI: 10.6084/m9.figshare.28767921
title: <i>WDJ-S4</i>, a standardized herbal formula, promotes gastrointestinal motility via modulation of the acetylcholine pathway in a loperamide-induced functional dyspepsia mice

description: WDJ-S4, a standardized herbal formula, has been prescribed for refractory functional dyspepsia (FD) in Korea, but the detailed mechanisms are lacking. The present study investigates the acceleration of gastrointestinal (GI) motility by WDJ-S4 and its potential mechanisms. For five days, WDJ-S4 (50, 100 and 200 mg/kg) or mosapride (3 mg/kg) was orally given to BALB/c mice. After 20 h of fasting, loperamide (10 mg/kg, i.p.) was given to the mice except for normal group. To assess gastric emptying or intestinal propulsion, 500 μL of 0.05% phenol red or 200 μL of 5% charcoal diet was given once orally. Loperamide delayed gastric emptying and intestinal propulsion, while WDJ-S4 ameliorated peristaltic dysfunction, evidenced by reductions of remaining phenol red in the stomach and a marked increase of charcoal propulsion in the intestine. WDJ-S4 also normalized levels of acetylcholine and acetylcholine-related enzymes, including choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), in the gastric antrum and jejunum. C-kit level and smooth muscle contraction-related genes were elevated by WDJ-S4 in both the gastric antrum and jejunum. Overall, WDJ-S4 can effectively promote GI motility. The efficacy is associated with modulation of acetylcholine pathway and the interstitial cells of Cajal (ICCs) activation. All the results provide scientific evidence supporting the clinical usage of WDJ-S4 for FD.
DOI: 10.6084/m9.figshare.28767921.v1
title: <i>WDJ-S4</i>, a standardized herbal formula, promotes gastrointestinal motility via modulation of the acetylcholine pathway in a loperamide-induced functional dyspepsia mice

description: WDJ-S4, a standardized herbal formula, has been prescribed for refractory functional dyspepsia (FD) in Korea, but the detailed mechanisms are lacking. The present study investigates the acceleration of gastrointestinal (GI) motility by WDJ-S4 and its potential mechanisms. For five days, WDJ-S4 (50, 100 and 200 mg/kg) or mosapride (3 mg/kg) was orally given to BALB/c mice. After 20 h of fasting, loperamide (10 mg/kg, i.p.) was given to the mice except for normal group. To assess gastric emptying or intestinal propulsion, 500 μL of 0.05% phenol red or 200 μL of 5% charcoal diet was given once orally. Loperamide delayed gastric emptying and intestinal propulsion, while WDJ-S4 ameliorated peristaltic dysfunction, evidenced by reductions of remaining phenol red in the stomach and a marked increase of charcoal propulsion in the intestine. WDJ-S4 also normalized levels of acetylcholine and acetylcholine-related enzymes, including choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), in the gastric antrum and jejunum. C-kit level and smooth muscle contraction-related genes were elevated by WDJ-S4 in both the gastric antrum and jejunum. Overall, WDJ-S4 can effectively promote GI motility. The efficacy is associated with modulation of acetylcholine pathway and the interstitial cells of Cajal (ICCs) activation. All the results provide scientific evidence supporting the clinical usage of WDJ-S4 for FD.
DOI: 10.6084/m9.figshare.30627898.v1
title: Potential pharmacological quality control markers in the traditional Japanese medicine Hangeshashinto: identifying anti-inflammatory ingredients through a cell-based bioassay and multicomponent analysis

description: The traditional Japanese medicine Hangeshashinto (HST) is a multicompound drug used for stomatitis. The identification of HST’s active ingredients is essential for understanding its mechanism of action and establishing pharmacological quality control markers, but remains unclear due to its multicomponent drug. To systematically explore anti-inflammatory ingredients in HST using a combined approach involving a cell-based bioassay and multicomponent analysis, and to identify potential quality marker compounds. A cell-based bioassay modeling stomatitis was established using human oral keratinocytes (HOK), with interleukin (IL)-1β–induced prostaglandin E2 (PGE2) as an inflammatory indicator. The PGE2 inhibitory effects of quality-controlled 101 HST manufacturing lots were compared. Multicomponent analysis was performed on the 101 HST samples, correlating the intensity of 121 component peaks with the pharmacological activities. Ingredients with the highest correlation coefficients were validated for their PGE2 inhibitory effects. A total of 101 HST samples (30 µg/mL: approximately IC<sub>50</sub>) showed consistent inhibition of IL-1β–induced PGE2 production in HOK (41.33%–67.38% with 100% as IL-1β). Correlation analysis between PGE2 inhibitory activities and peak intensity of 121 components revealed the contribution of each ingredient to the pharmacological effect. Eight ingredients (glycycoumarin, neoglycyrol, [6]-shogaol, [8]-shogaol, [10]-shogaol, [6]-gingerol, [8]-gingerol, and [10]-gingerol) with the highest correlation coefficients (below −0.30) exhibited PGE2-inhibitory potential. The standardization of current quality control markers contributes to the stability of HST’s anti-inflammatory effects. The eight components discovered by this integrated analysis method may become novel quality control marker ingredients for further improving the pharmacological quality of HST.
DOI: 10.6084/m9.figshare.30657843
title: An exploratory evaluation of the interaction risk between herbal products and pharmaceutical medicines used concurrently for disease management in Blantyre, Malawi

description: The use of herbal products in Malawi remains widespread and culturally significant, often occurring alongside pharmaceutical medicine treatments. As the burden of non-communicable diseases such as diabetes and hypertension continues to rise, the potential for herbal-drug interactions (HDIs) represents an underexamined public health concern. Evaluate the concurrent use of herbal products and pharmaceutical medicines among patients with diabetes or hypertension in a large health care facility in Malawi and identify potential adverse HDIs. An exploratory mixed-methods, cross-sectional study was conducted with 301 patients attending a diabetes or hypertension clinic at Queen Elizabeth Central Hospital in Blantyre, Malawi. Participants self-reported herbal and pharmaceutical use, and a targeted literature review was undertaken to assess potential pharmacokinetic and pharmacodynamic interactions between commonly reported herbal products and prescribed medications. Participants reported concurrent use of a wide variety of herbal products (e.g., garlic, ginger, okra, lemon, mango, moringa) with prescription medicines (e.g., metformin, insulin, glibenclamide, hydrochlorothiazide, enalapril, amlodipine). While clinical outcomes were not independently verified, literature review findings, in some cases, indicated meaningful potential for HDIs. This study provides foundational data on herbal-pharmaceutical co-use in Malawi and highlights the need for expanded research, improved documentation of herbal use in healthcare settings, and improved education for patients and providers. Integrating awareness of herbal product use into clinical care is essential, and the methodology and findings may inform future hypothesis-driven studies across Africa and other regions where traditional and modern medicine use overlaps.
DOI: 10.6084/m9.figshare.30657843.v1
title: An exploratory evaluation of the interaction risk between herbal products and pharmaceutical medicines used concurrently for disease management in Blantyre, Malawi

description: The use of herbal products in Malawi remains widespread and culturally significant, often occurring alongside pharmaceutical medicine treatments. As the burden of non-communicable diseases such as diabetes and hypertension continues to rise, the potential for herbal-drug interactions (HDIs) represents an underexamined public health concern. Evaluate the concurrent use of herbal products and pharmaceutical medicines among patients with diabetes or hypertension in a large health care facility in Malawi and identify potential adverse HDIs. An exploratory mixed-methods, cross-sectional study was conducted with 301 patients attending a diabetes or hypertension clinic at Queen Elizabeth Central Hospital in Blantyre, Malawi. Participants self-reported herbal and pharmaceutical use, and a targeted literature review was undertaken to assess potential pharmacokinetic and pharmacodynamic interactions between commonly reported herbal products and prescribed medications. Participants reported concurrent use of a wide variety of herbal products (e.g., garlic, ginger, okra, lemon, mango, moringa) with prescription medicines (e.g., metformin, insulin, glibenclamide, hydrochlorothiazide, enalapril, amlodipine). While clinical outcomes were not independently verified, literature review findings, in some cases, indicated meaningful potential for HDIs. This study provides foundational data on herbal-pharmaceutical co-use in Malawi and highlights the need for expanded research, improved documentation of herbal use in healthcare settings, and improved education for patients and providers. Integrating awareness of herbal product use into clinical care is essential, and the methodology and findings may inform future hypothesis-driven studies across Africa and other regions where traditional and modern medicine use overlaps.
DOI: 10.6084/m9.figshare.30335867
title: Indirubin regulates M1/M2 polarization and inhibits ferroptosis in dextran sulfate sodium induced colitis and in cultured THP-1 cells

description: Macrophages play a critical role in the pathogenesis of ulcerative colitis (UC). Indirubin (IDR), a natural ligand of the aryl hydrocarbon receptor (AhR), has been shown to ameliorate DSS-induced colitis in our previous study (Liu Z et al.). To investigate whether IDR exerts its protective effects by regulating M1/M2 polarization and inhibiting ferroptosis in macrophages. Immunohistochemistry staining targeting CD206 and F4/80 was performed to evaluate the effect of IDR on the polarization of M1/M2 macrophages in colitis. Subsequently, the effects of IDR on the M1- or M2-polarization of THP-1-derived macrophages were investigated. Furthermore, the effects of IDR on ferroptosis in the colon tissue of mice and on RSL3-induced ferroptosis in THP-1-derived macrophages were assessed. The results were verified in mouse peritoneal macrophages. In addition to reducing the infiltrated macrophages, IDR treatment preserved CD206+ macrophages in DSS-induced colitis. Using cultured THP-1 cells, we demonstrated that IDR inhibited M1 polarization and prompted M2 polarization. Furthermore, we showed that IDR treatment decreased levels of 4-HNE while increasing GPX4 and NRF2 in DSS-induced colitis and THP-1 cells. IDR treatments also reduced cellular reactive oxygen species (ROS) and iron content, and mitigated RSL3-induced ferroptosis in THP-1-derived macrophages. Similarly, IDR augmented M2-polarization and alleviated ferroptosis in peritoneal macrophages. IDR skews the polarization of macrophages from M1 to M2. Furthermore, it inhibits ferroptosis in both mice and THP-1-derived macrophages. These mechanisms may contribute to the therapeutic effects of IDR in the treatment of UC.
DOI: 10.6084/m9.figshare.30335867.v1
title: Indirubin regulates M1/M2 polarization and inhibits ferroptosis in dextran sulfate sodium induced colitis and in cultured THP-1 cells

description: Macrophages play a critical role in the pathogenesis of ulcerative colitis (UC). Indirubin (IDR), a natural ligand of the aryl hydrocarbon receptor (AhR), has been shown to ameliorate DSS-induced colitis in our previous study (Liu Z et al.). To investigate whether IDR exerts its protective effects by regulating M1/M2 polarization and inhibiting ferroptosis in macrophages. Immunohistochemistry staining targeting CD206 and F4/80 was performed to evaluate the effect of IDR on the polarization of M1/M2 macrophages in colitis. Subsequently, the effects of IDR on the M1- or M2-polarization of THP-1-derived macrophages were investigated. Furthermore, the effects of IDR on ferroptosis in the colon tissue of mice and on RSL3-induced ferroptosis in THP-1-derived macrophages were assessed. The results were verified in mouse peritoneal macrophages. In addition to reducing the infiltrated macrophages, IDR treatment preserved CD206+ macrophages in DSS-induced colitis. Using cultured THP-1 cells, we demonstrated that IDR inhibited M1 polarization and prompted M2 polarization. Furthermore, we showed that IDR treatment decreased levels of 4-HNE while increasing GPX4 and NRF2 in DSS-induced colitis and THP-1 cells. IDR treatments also reduced cellular reactive oxygen species (ROS) and iron content, and mitigated RSL3-induced ferroptosis in THP-1-derived macrophages. Similarly, IDR augmented M2-polarization and alleviated ferroptosis in peritoneal macrophages. IDR skews the polarization of macrophages from M1 to M2. Furthermore, it inhibits ferroptosis in both mice and THP-1-derived macrophages. These mechanisms may contribute to the therapeutic effects of IDR in the treatment of UC.
DOI: 10.6084/m9.figshare.30571464
title: Dose-response assessment of neuroactive botanical extracts and their bioactive constituents using microelectrode array (MEA) recordings in rat primary cortical cultures

description: Use of botanicals is increasing. While often considered as safe, neuromodulatory effects have been demonstrated previously. Establish the neuroactive potential of 13 botanical extracts. For 8 of these, we made a direct comparison with their major constituent. We used microelectrode array (MEA) recordings of primary rat cortical cultures to evaluate dose-response relationships on neuronal network function <i>in vitro</i>. Exposure to extracts from milk thistle, usnea, green tea, aristolochia, and ephedra mildly inhibited neuronal activity with distinct neuronal activity phenotypes. Extracts of tripterygium, yohimbe, kratom, and kava strongly inhibited neuronal activity. Despite differences in the degree of inhibition, all inhibitory extracts show No Observed Effect Levels (NOELs) of 1–5 µg/mL. Exposure to aconite, blue cohosh, goldenseal and oleander induced specific activity phenotypes characterized by hyperexcitation and/or intensification of (network) burst activity. While the extracts exhibit a narrow effective dose range, the extracts from aconite, goldenseal and oleander are most potent with NOELs of 0.25–0.5 µg/mL. Silybin B (milk thistle), epigallocatechin gallate (green tea), yohimbine (yohimbe), dihydrokavain (kava), mitragynine (kratom), aconitine (aconite), berberine (goldenseal) and oleandrin (oleander) were tested to investigate if the distinct neuronal activity phenotypes, indicative for the presence of multiple modes of action, are due to the known bioactive constituents of the extracts. For most constituents the activity phenotype is comparable to the extract, although the extract generally has a higher potency. Botanical extracts and constituents evoke diverse activity phenotypes, highlighting the complexity of hazard characterization of botanicals.
DOI: 10.6084/m9.figshare.30571464.v1
title: Dose-response assessment of neuroactive botanical extracts and their bioactive constituents using microelectrode array (MEA) recordings in rat primary cortical cultures

description: Use of botanicals is increasing. While often considered as safe, neuromodulatory effects have been demonstrated previously. Establish the neuroactive potential of 13 botanical extracts. For 8 of these, we made a direct comparison with their major constituent. We used microelectrode array (MEA) recordings of primary rat cortical cultures to evaluate dose-response relationships on neuronal network function <i>in vitro</i>. Exposure to extracts from milk thistle, usnea, green tea, aristolochia, and ephedra mildly inhibited neuronal activity with distinct neuronal activity phenotypes. Extracts of tripterygium, yohimbe, kratom, and kava strongly inhibited neuronal activity. Despite differences in the degree of inhibition, all inhibitory extracts show No Observed Effect Levels (NOELs) of 1–5 µg/mL. Exposure to aconite, blue cohosh, goldenseal and oleander induced specific activity phenotypes characterized by hyperexcitation and/or intensification of (network) burst activity. While the extracts exhibit a narrow effective dose range, the extracts from aconite, goldenseal and oleander are most potent with NOELs of 0.25–0.5 µg/mL. Silybin B (milk thistle), epigallocatechin gallate (green tea), yohimbine (yohimbe), dihydrokavain (kava), mitragynine (kratom), aconitine (aconite), berberine (goldenseal) and oleandrin (oleander) were tested to investigate if the distinct neuronal activity phenotypes, indicative for the presence of multiple modes of action, are due to the known bioactive constituents of the extracts. For most constituents the activity phenotype is comparable to the extract, although the extract generally has a higher potency. Botanical extracts and constituents evoke diverse activity phenotypes, highlighting the complexity of hazard characterization of botanicals.
DOI: 10.6084/m9.figshare.29877428
title: Uncovering the mechanistic basis of <i>Rheum palmatum</i> L. (rhubarb) in the treatment of chronic kidney disease: an integrative approach using network pharmacology, molecular docking, and experimental validation

description: <i>Rheum palmatum</i> L. (Rhubarb) has shown potential in managing Chronic Kidney Disease (CKD) but its protective mechanisms remain unclear. This study investigates rhubarb’s therapeutic effects and underlying mechanisms in CKD. High-performance liquid chromatography (HPLC) established a rhubarb fingerprint to ensure quality control. Network pharmacology and Mendelian randomization identified primary CKD therapeutic targets. Inflammation, oxidative stress, and renal performance were assessed through ELISAs and biochemical tests. Renal structure and fibrosis were examined using hematoxylin-eosin and Masson staining. Protein expression related to fibrosis, apoptosis, and NF-κB pathway activity was measured <i>via</i> Western blotting. Discovery Studio 2019 (DS 2019) was used for molecular docking. HPLC fingerprinting confirmed high batch-to-batch consistency of rhubarb, identifying five key anthraquinones (aloe-emodin, rhein, emodin, chrysophanol, physcion) with similarity indices &gt;0.91. Network pharmacology identified 19 active compounds targeting 2,597 CKD-related proteins, with 47 overlapping targets including IL6, TNF, TP53, CASP3, and IL1B as core nodes. MR analysis demonstrated a statistically significant causal association between TNF and CKD (OR = 1.02, <i>p</i> &lt; 0.05), with positive trends for IL6 and CASP3. In CKD rat models, rhubarb significantly improved renal function by reducing blood urea nitrogen (BUN), serum creatinine (SCr), and uric acid (UA) levels (<i>p</i> &lt; 0.05). Histopathology showed reduced glomerulosclerosis, tubular atrophy, interstitial fibrosis, and inflammatory infiltration after treatment. Rhubarb markedly decreased renal fibrosis markers including collagen I, collagen III, α-SMA, and TGF-β (<i>p</i> &lt; 0.01). Pro-inflammatory cytokines IL-6, IL-1β, and TNF-α levels were significantly suppressed (<i>p</i> &lt; 0.001). Antioxidant enzyme activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were restored, while lipid peroxidation (LPO) was reduced (<i>p</i> &lt; 0.05). Rhubarb inhibited NF-κB pathway activation by lowering phosphorylated NF-κB and IκBα, and increasing total IκBα expression (<i>p</i> &lt; 0.01). Apoptosis-related proteins showed upregulated Bcl-2 and downregulated Bax and cleaved caspase-3 expression (<i>p</i> &lt; 0.05). Molecular docking confirmed strong binding affinities of rhubarb’s core compounds with key targets such as TNF and IL6, supporting their therapeutic roles. Rhubarb significantly reduces renal impairment, fibrosis, inflammation, and apoptosis through the NF-κB pathway, supporting its traditional use and potential as an adjunct therapy for CKD.