Lesión hepática inducida por Phyllanthus niruri (chancapiedra), un remedio natural para urolitiasis / Liver injury induced by Phyllanthus niruri (chancapiedra), a natural remedy for urolithiasis

Tanto la lesión hepática inducida por drogas (DILI), así como la lesión hepática inducida por hierbas (HILI), son una preocupación creciente en la atención sanitaria contemporánea que plantea importantes desafíos clínicos debido a sus variadas etiologías, presentaciones clínicas y posibles resultados potencialmente mortales. Presentamos el caso de un paciente masculino de 38 años con antecedentes de cálculos renales que consultó por dolor lumbar y hematuria. Al ingreso presentó ictericia, hepatomegalia, dolor a la palpación en fosa ilíaca derecha y no tenía signos de hepatopatía crónica, con pruebas de función hepática anormales, que mostraron un patrón hepatocelular asociado con hiperbilirrubinemia. Se descartó obstrucción biliar, trombosis portal, hepatitis autoinmune y viral, con panel autoinmune negativo. El paciente refirió haber consumido un remedio herbario para los cálculos renales llamado "vino rompe cálculos (chancapiedra)", que se supone contiene Phyllanthus niruri, cinco días antes del inicio de los síntomas. Una biopsia hepática reveló hepatitis aguda con infiltrado inflamatorio mixto. Debido al empeoramiento de las pruebas de función hepática y la sospecha de DILI idiosincrásico, se inició un ensayo terapéutico con corticosteroides, que resultó en una mejoría clínica y del perfil hepático. La gravedad de este caso nos recuerda la necesidad de incrementar el seguimiento por parte de las autoridades reguladoras de medicamentos, implementar campañas educativas para los pacientes e informar a la comunidad sobre productos con alertas activas.

Both drug-induced liver injury (DILI) and herb-induced liver injury (HILI) are a growing concern in contemporary healthcare that poses significant clinical challenges due to their varied etiology, clinical presentations, and potential life-threatening outcomes. We present the case of a 38-year-old male patient with a history of kidney stones who consulted for low back pain and hematuria. On admission he presented with jaundice, hepatomegaly, pain on palpation in the right iliac fossa and no signs of chronic liver disease, with abnormal liver function tests, which showed a hepatocellular pattern associated with hyperbilirubinemia. Biliary obstruction, portal thrombosis, autoimmune and viral hepatitis were ruled out, with negative autoimmune panel. The patient reported consuming an herbal remedy for kidney stones called "stone-breaking wine (chancapiedra)", presumed to contain Phyllanthus niruri, five days before the onset of symptoms. A liver biopsy revealedacute hepatitis with mixed inflammatory infiltrate. Due to worsening liver function tests and suspicion of idiosyncratic DILI, a therapeutic trial with corticosteroids was initiated, which resulted in clinical and liver profile improvement. The severity of this case reminds us of the need to increase follow-up by drug regulatory authorities, implement educational campaigns for patients, and inform the community about products with active alerts.

Herbal remedies in the management of hyperuricemia and gout: A review of in vitro, in vivo and clinical evidences.

Gout, or hyperuricemia is a multifactorial and multi-faceted metabolic disease that is quite difficult to manage and/or treat. Conventional therapies such as non-steroidal anti-inflammatory drugs (NSAIDs) such as allopurinol, corticosteroids and colchicine amongst others, have helped in its management and treatment to some extent. This study aimed to compile and analyze the different herbal remedies used in the management of hyperuricemia and gout. A literature search was conducted from key databases (PubMed, ScienceDirect, Cochrane Library, Google Scholar) using relevant keywords via the PRISMA model. Smilax riparia A.DC. from Traditional Chinese Medicine is used in many countries for its therapeutic effect on lowering serum urate levels. No single study was able to establish the efficacy of a specific traditionally used herb via in vitro, in vivo, and clinical studies. Patients were found to use a panoply of natural remedies, mainly plants to treat hyperuricemia and gout, which have been validated to some extent by in vitro, in vivo, and clinical studies. Nonetheless, further research is needed to better understand the ethnopharmacological relationship of such herbal remedies.

Use of Japanese Herbal Kampo Medicine in Patients With Acute Cardiovascular Disease　- A 12-Year Nationwide Cohort Analysis.

BACKGROUND: Kampo, a Japanese herbal medicine, is approved for the treatment of various symptoms/conditions under national medical insurance coverage in Japan. However, the contemporary nationwide status of Kampo use among patients with acute cardiovascular diseases remains unknown. METHODS AND RESULTS: Using the Japanese Diagnosis Procedure Combination database, we retrospectively identified 2,547,559 patients hospitalized for acute cardiovascular disease (acute myocardial infarction, heart failure, pulmonary embolism, or aortic dissection) at 1,798 hospitals during the fiscal years 2010-2021. Kampo medicines were used in 227,008 (8.9%) patients, with a 3-fold increase from 2010 (4.3%) to 2021 (12.4%), regardless of age, sex, disease severity, and primary diagnosis. The top 5 medicines used were Daikenchuto (29.4%), Yokukansan (26.1%), Shakuyakukanzoto (15.8%), Rikkunshito (7.3%), and Goreisan (5.5%). From 2010 to 2021, Kampo medicines were initiated earlier during hospitalization (from a median of Day 7 to Day 3), and were used on a greater proportion of hospital days (median 16.7% vs. 21.4%). However, the percentage of patients continuing Kampo medicines after discharge declined from 57.9% in 2010 to 39.4% in 2021, indicating their temporary use. The frequency of Kampo use varied across hospitals, with the median percentage of patients prescribed Kampo medications increasing from 7.7% in 2010 to 11.5% in 2021. CONCLUSIONS: This nationwide study demonstrates increasing Kampo use in the management of acute cardiovascular diseases, warranting further pharmacoepidemiological studies on its effectiveness.

Antioxidative and Anti-inflammatory Effects of Plant-derived Hypoglycemic Medicines: An In vivo/In vitro Systematic Review.

BACKGROUND: The activation of oxidative stress and inflammatory conditions has been associated with acceleration in diabetes (DM) onset and complications. Despite various anti-DM medications, there is a growing trend to discover inexpensive and effective treatments with low adverse effects from plants as one of the promising sources for drug development. OBJECTIVE: This study aimed to systematically investigate the simultaneous anti-inflammatory and antioxidant effects of plant-derived hypoglycemic medicines in diabetic experimental models. METHODS: The search terms consisted of "diabetes", "herbal medicine", "antioxidant", "Inflammatory biomarker", and their equivalents among PubMed, Scopus, Web of Science, and Cochrane Library databases up to 17 August 2021. RESULTS: Throughout the search of databases, 201 eligible experimental studies were recorded. The results showed that the most commonly assessed inflammatory and oxidative stress biomarkers were tumor necrosis factor (TNF)-α, interleukin (IL) 6, IL-1ß, IL-10, malondialdehyde (MDA), and nitric oxide (NO). The activity of antioxidant enzymes, including superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) were assessed in the present review. Among herbal treatments, Trigonella foenum-graecum L., Centella asiatica (L.) Urb., Vitis vinifera L., and Moringa oleifera Lam. were most commonly used for diabetic complications. Due to the dispersion of the treatments, meta-analysis was not applicable. CONCLUSION: Our findings showed that the application of different plant-derived hypoglycemic treatments in animal models improved diabetes and its complications, as well as modulated concomitant inflammatory and oxidative stress biomarkers. These findings suggest that plant-based antidiabetic medicines and food supplements have the potential to manage diabetes and its complications.

Urtica pilulifera L. seed extract promotes folliculogenesis and alleviates the diminished ovarian reserve in the Balb/c mice model: An experimental study.

Background: Urtica pilulifera L. seed (UPS) is a Persian traditional medicine prescription that positively affects female infertility. Objective: This study aimed to evaluate the beneficial effects of UPS on a diminished ovarian reserve (DOR) model induced by cyclophosphamide in Balb/c mice. Materials and Methods: A single intraperitoneal (75 mg/kg) of cyclophosphamide was administered to establish a DOR model. 25 female Balb/c mice (6-8 wk, 25 ± 2 gr) were randomly divided into 5 groups (n = 5/each), including control (normal saline), model (DOR), DOR+50, DOR+100, and DOR+200 (mg/kg UPS, gavage) groups for 14 days. The levels of follicle-stimulating hormone, luteinizing hormone, estradiol, malondialdehyde, superoxide dismutases, apoptosis, and histopathological alterations were analyzed. Gas chromatography-mass spectrometry analysis was performed to identify the phytochemicals of the UPS. Results: It was observed that the UPS extract reduced malondialdehyde concentration and apoptosis in the DOR model as well as enhanced superoxide dismutases activity in the ovaries in a dose-dependent manner. Moreover, it exerted a modulatory effect on steroidal hormones such as follicle-stimulating hormone, luteinizing hormone, and estradiol. The histopathological analysis revealed the therapeutic potential of the UPS extract. The main chemical components of UPS were linoleic acid (59.25%), n-hexadecanoic acid (10.36%), and oleic acid (8.29%). Conclusion: The results indicated that the UPS extract has therapeutic potential in the DOR model. This potential is attributed to the reduction of oxidative stress, modulation of apoptosis, and regulation of steroidal hormones that may be associated with the observed beneficial effects of fatty acids on fertility improvement.

Chinese herbal medicines for the treatment of depression: a systematic review and network meta-analysis.

Objectives: Amidst rising global burden of depression and the associated challenges with conventional antidepressant therapies, there is a growing interest in exploring the efficacy and safety of alternative treatments. This study uses a Bayesian network meta-analysis to rigorously evaluate the therapeutic potential of Chinese herbal medicines in the treatment of depression, focusing on their comparative efficacy and safety against standard pharmacological interventions. Methods: Five databases (PubMed, Wanfang Data, EMBASE, CNKI, and the Cochrane Library) and grey literature were searched from inception to end of July 2023 to identify studies that assessed the efficacy and safety of Chinese herbal medicines in treating depression. The response rate, Hamilton Depression Scale (HAMD) scores, and rates of adverse events were assessed through both direct and indirect comparisons. Data extraction and risk of bias assessment were meticulously performed. Statistical analysis used Markov chain Monte Carlo methods, with effect size estimates provided as odd ratios and their 95% confidence intervals. Results: A total of 198 RCTs involving 8,923 patients were analyzed, assessing 17 Chinese herbal medicines. Surface Under the Cumulative Ranking results indicated that the top three treatments with the best response rate were possibly Guipiwan, Ease Pill, and Chaihu Jia Longgu Muli Decoction; the top three treatments on the reduction of HAMD scores were Chai Hu Shu Gan San, Xingnao Jieyu Decoction, and Xiaoyao Powder; and the top three treatments with the lowest adverse effects rates were Xiaoyao Powder, Alprazolam, and Xingnao Jieyu Decoction. Interestingly, commonly used synthetic drugs such as Fluoxetine, Escitalopram, Amitriptyline, Sertraline, Flupentixol and Melitracen, and Venlafaxine, not only appeared to be less effective than specific Chinese herbal medicines (Gan Mai Da Zao Decoction, Chaihu Jia Longgu Muli Decoction, Chai Hu Shu Gan San, Danzhi-Xiaoyao-San, and Xingnao Jieyu Decoction), but they were also related to substantially higher risk of adverse events. Conclusion: Our findings elucidate the promising therapeutic potential of Chinese herbal medicines as viable alternatives in the treatment of depression, with certain herbs demonstrating enhanced efficacy and safety profiles. The outcomes of this study advocate for the integration of these alternative modalities into contemporary depression management paradigms. However, it underscores the necessity for larger, methodologically robust trials to further validate and refine these preliminary findings. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023452109.

Traditional herbal medicine: Therapeutic potential in acute gouty arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute gouty arthritis (AGA) is characterized by a rapid inflammatory reaction caused by the build-up of monosodium urate (MSU) crystals in the tissues surrounding the joints. This condition often associated with hyperuricemia (HUA), is distinguished by its symptoms of intense pain, active inflammation, and swelling of the joints. Traditional approaches in AGA management often fall short of desired outcomes in clinical settings. However, recent ethnopharmacological investigations have been focusing on the potential of Traditional Herbal Medicine (THM) in various forms, exploring their therapeutic impact and targets in AGA treatment. AIM OF THE REVIEW: This review briefly summarizes the current potential pharmacological mechanisms of THMs - including active ingredients, extracts, and prescriptions -in the treatment of AGA, and discusses the relevant potential mechanisms and molecular targets in depth. The objective of this study is to offer extensive information and a reference point for the exploration of targeted AGA treatment using THMs. MATERIALS AND METHODS: This review obtained scientific publications focused on in vitro and in vivo studies of anti-AGA THMs conducted between 2013 and 2023. The literature was collected from various journals and electronic databases, including PubMed, Elsevier, ScienceDirect, Web of Science, and Google Scholar. The retrieval and analysis of relevant articles were guided by keywords such as "acute gouty arthritis and Chinese herbal medicine," "acute gouty arthritis herbal prescription," "acute gouty arthritis and immune cells," "acute gouty arthritis and inflammation," "acute gouty arthritis and NOD-like receptor thermoprotein domain associated protein 3 (NLRP3)," "acute gouty arthritis and miRNA," and "acute gouty arthritis and oxidative stress." RESULTS: We found that AGA has a large number of therapeutic targets, highlighting the effectiveness the potential of THMs in AGA treatment through in vitro and in vivo studies. THMs and their active ingredients can mitigate AGA symptoms through a variety of therapeutic targets, such as influencing macrophage polarization, neutrophils, T cells, natural killer (NK) cells, and addressing factors like inflammation, NLRP3 inflammasome, signaling pathways, oxidative stress, and miRNA multi-target interactions. The anti-AGA properties of THMs, including their active components and prescriptions, were systematically summarized and categorized based on their respective therapeutic targets. CONCLUSION: phenolic, flavonoid, terpenoid and alkaloid compounds in THMs are considered the key ingredients to improve AGA. THMs and their active ingredients achieve enhanced efficacy through interactions with multiple targets, of which NLRP3 is a main therapeutic target. Nonetheless, given the intricate composition of traditional Chinese medicine (TCM), additional research is required to unravel the underlying mechanisms and molecular targets through which THMs alleviate AGA.

Exploring the therapeutic potential of tonic Chinese herbal medicine for gynecological disorders: An updated review.

ETHNOPHARMACOLOGICAL RELEVANCE: Gynecological disorders have the characteristics of high incidence and recurrence rate, which sorely affects female's health. Since ancient times, traditional Chinese medicine (TCM), especially tonic medicine (TM), has been used to deal with gynecological disorders and has unique advantages in effectiveness and safety. AIM OF THE REVIEW: In this article, we aim to summarize the research progress of TMs in-vivo and in-vitro, including their formulas, single herbs, and compounds, for gynecological disorders treatment in recent years, and to offer a reference for further research on the treatment of gynecological disorders and their clinical application in the treatment of TMs. MATERIALS AND METHODS: Relevant information on the therapeutic potential of TMs against gynecological disorders was collected from several scientific databases including Web of Science, PubMed, CNKI, Google Scholar and other literature sources. RESULTS: So far, there are 46 different formulas, 3 single herbs, and 24 compounds used in the treatment of various gynecological disorders such as premature ovarian failure, endometriosis breast cancer, and so on. Many experimental results have shown that TMs can regulate apoptosis, invasion, migration, oxidative stress, and the immune system. In addition, the effect of TMs in gynecological disorders treatment may be due to the regulation of VEGF, PI3K-AKT, MAPK, NF-κB, and other signaling pathways. Apparently, TMs play an active role in the treatment of gynecological disorders by regulating these signaling pathways. CONCLUSION: TMs have a curative effect on the prevention and treatment of gynecological disorders. It could relieve and treat gynecological disorders through a variety of pathways. Therefore, the appropriate TM treatment program makes it more possible to treat gynecological disorders.

Effects of natural extract interventions in prostate cancer: A systematic review and network meta-analysis.

BACKGROUND: Over years, there has been a widespread quest for effective dietary patterns and natural extracts to mitigate prostate cancer risk. However, despite numerous experimental studies conducted on various natural extracts, the evidence substantiating their efficacy remains largely insufficient. This dearth of compelling evidence presents a significant challenge in advocating for their widespread use as preventive measures against prostate cancer. OBJECTIVE: Our study endeavors to undertake a network meta-analysis to evaluate the influence of natural extracts on prostate cancer. METHODS: Researchers systematically searched through Embase, PubMed, Cochrane Library, and Web of Science databases until December 2023. The main focus was on assessing primary outcomes comprising prostate-specific antigen (PSA), insulin-like growth factor-binding protein-3 (IGFBP-3), insulin-like growth factor-1 (IGF-1). We conducted data analysis utilizing StataMP 15.0 software. Therapeutic effects were ranked based on the probability values derived from Surface Under the Cumulative Ranking curve (SUCRA). Additionally, cluster analysis was employed to assess the impacts of natural extracts on three distinct outcomes. RESULTS: Following screening procedures, the 28 eligible studies were incorporated, the selected studies encompassed 1,566 prostate cancer patients and evaluated 16 different natural extract treatments. Specifically, 24 trials included PSA indicators, 10 included IGF-1 indicators, and 8 included IGFBP-3 indicators. The findings revealed that, based on the SUCRA values, the combined therapy of silybin with selenium (74%) appears to be the most effective approach for reducing serum PSA levels. Simultaneously, silybin alone (84.6%) stands out as the most promising option for decreasing serum IGF-1 levels. Lastly, concerning IGFBP-3, silybin alone (67.7%) emerges as the optimal choice. Twelve studies provided comprehensive information on adverse drug reactions/events (ADR/ADE), whereas five articles did not report any significant ADR/ADE. CONCLUSION: The NMA suggests that, compared to placebo, utilizing silybin either alone or in combination with selenium has been shown to enhance therapeutic effects, offering potential benefits to patients with prostate cancer. This study can offer valuable insights for prostate patients considering natural extract treatments. Further evidence is required to confirm the safety profile of these treatments.

Research progress of the mechanisms and applications of ginsenosides in promoting bone formation.

BACKGROUND: Bone deficiency-related diseases caused by various factors have disrupted the normal function of the skeleton and imposed a heavy burden globally, urgently requiring potential new treatments. The multi-faceted role of compounds like ginsenosides and their interaction with the bone microenvironment, particularly osteoblasts can promote bone formation and exhibit anti-inflammatory, vascular remodeling, and antibacterial properties, holding potential value in the treatment of bone deficiency-related diseases and bone tissue engineering. PURPOSE: This review summarizes the interaction between ginsenosides and osteoblasts and the bone microenvironment in bone formation, including vascular remodeling and immune regulation, as well as their therapeutic potential and toxicity in the broad treatment applications of bone deficiency-related diseases and bone tissue engineering, to provide novel insights and treatment strategies. METHODS: The literature focusing on the mechanisms and applications of ginsenosides in promoting bone formation before March 2024 was searched in PubMed, Web of Science, Google Scholar, Scopus, and Science Direct databases. Keywords such as "phytochemicals", "ginsenosides", "biomaterials", "bone", "diseases", "bone formation", "microenvironment", "bone tissue engineering", "rheumatoid arthritis", "periodontitis", "osteoarthritis", "osteoporosis", "fracture", "toxicology", "pharmacology", and combinations of these keywords were used. RESULTS: Ginsenoside monomers regulate signaling pathways such as WNT/ß-catenin, FGF, and BMP/TGF-ß, stimulating osteoblast generation and differentiation. It exerts angiogenic and anti-inflammatory effects by regulating the bone surrounding microenvironment through signaling such as WNT/ß-catenin, NF-κB, MAPK, PI3K/Akt, and Notch. It shows therapeutic effects and biological safety in the treatment of bone deficiency-related diseases, including rheumatoid arthritis, osteoarthritis, periodontitis, osteoporosis, and fractures, and bone tissue engineering by promoting osteogenesis and improving the microenvironment of bone formation. CONCLUSION: The functions of ginsenosides are diverse and promising in treating bone deficiency-related diseases and bone tissue engineering. Moreover, potential exists in regulating the bone microenvironment, modifying biomaterials, and treating inflammatory-related bone diseases and dental material applications. However, the mechanisms and effects of some ginsenoside monomers are still unclear, and the lack of clinical research limits their clinical application. Further exploration and evaluation of the potential of ginsenosides in these areas are expected to provide more effective methods for treating bone defects.

Chinese herbal medicine bath therapy for psoriasis vulgaris using topical calcipotriol as the comparator: A systematic review with meta-analysis and association rule analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoriasis is a chronic inflammatory skin disease. Vitamin D analogues are the first-line topical agents for the long-term management of psoriasis. Chinese herbal medicine (CHM) bath therapy is commonly employed for psoriasis. However, the effects and safety of CHM bath therapy for psoriasis vulgaris, using topical calcipotriol as the comparator, remain inconclusive. Furthermore, the combination of herbs, a distinctive feature of CHM, is essential for its therapeutic effects due to the individual and synergistic properties of the herbs involved. AIM OF THE STUDY: The review was conducted to evaluate the effectiveness and safety of CHM bath therapy for psoriasis vulgaris, using calcipotriol as the comparator. Potential herbs and herb combinations of CHM bath therapy were also explored for further drug discovery. MATERIALS AND METHODS: Nine databases were searched from inception until March 05, 2024. Randomised controlled trials (RCTs) investigating CHM bath therapy, using calcipotriol as the comparator, were included. Statistical analyses were performed using RevMan 5.4, Stata 12.0 and SPSS Clementine 12.0 software. The evidence certainty for outcomes was assessed using the approach proposed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group. Moreover, association rule analysis on herbs identified in the systematic review was conducted to explore the potential herbs and herb combinations. RESULTS: A total of 17 RCTs involving 1,379 participants were included in this systematic review. The findings of this review revealed that: 1) CHM bath therapy produced comparable effects to calcipotriol in reducing Psoriasis Area and Severity Index (PASI), Psoriasis Scalp Severity Index (PSSI), and itch visual analogue scale (VAS) at the end of the treatment phase; as well as exhibited a superior long-term effect than calcipotriol through decreasing relapse rates at the end of the follow-up phase; 2) CHM bath therapy showed an additional benefit when combined with calcipotriol in managing psoriasis vulgaris at the end of the treatment phase, in terms of PASI, PSSI, itch VAS, IL-17, IL-23, CD3+ and CD4+ T cells. The certainty of the evidence was rated as 'very low', 'low' or 'moderate' based on the GRADE assessment, considering some concerns or high risk of bias of included studies, substantial heterogeneity, and existing publication bias of some outcomes. Additionally, the proportions of participants reporting adverse events were similar in both groups. Association rule analysis of all included herbs identified 23 herb combinations including Prunus persica (L.) Batsch and Carthamus tinctorius L., as well as 11 frequently used herbs, such as Kochia scoparia (L.) Schrad., Dictamnus dasycarpus Turcz. And Sophora flavescens Ait. CONCLUSIONS: The effects of CHM bath therapy were comparable with those of topical calcipotriol but demonstrated a longer-lasting effect. Combining CHM bath therapy with calcipotriol also provided an additional benefit for adult psoriasis vulgaris. However, the certainty of the evidence was downgraded due to the methodological limitations of included studies. To confirm the findings of this review, future investigations should involve double-blinded, placebo-controlled RCTs. Importantly, it appears worthwhile to consider further research for drug development utilising the identified herbs or herb combinations.

Cycasin derivative: a potential embryotoxic component of Atractylodes macrocephala rhizome for limb malformation.

Objective: The rhizome of Atractylodes macrocephala Koidz. (Asteraceae), called Atractylodes macrocephala rhizome (AMR) and known by its traditional name Bai Zhu, is a prominent Chinese herbal medicine employed for preventing miscarriage. However, our previous study revealed that high dosages of AMR administered during pregnancy could cause embryotoxicity but the specific embryotoxic components and their underlying mechanisms remain unclear. This study aimed to screen and identify the potential embryotoxic components of AMR. Methods: The AMR extracts and sub-fractions were analyzed by thin layer chromatography and subsequently screened by in vitro mouse limb bud micromass and mouse whole embryo culture bioassays. The embryotoxic fractions from AMR were further evaluated in vivo using a pregnant mouse model. The structures of the potential embryotoxic components were analyzed using matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). Results: In vitro and in vivo bioassays revealed that AMR glycoside-enriched sub-fractions (AMR-A-IIa and AMR-A-IIb) exhibited potential embryotoxicity. These sub-fractions, when administered to pregnant animals, increased the incidence of stillbirth and congenital limb malformations. MS spectrometry analysis identified cycasin derivatives in both sub-fractions, suggesting their possible role in the observed limb malformations. However, further experiments are necessary to validate this hypothesis and to elucidate the underlying mechanisms. Conclusions: Our study provides significant scientific evidence on the pharmacotoxicity of AMR, which is important for the safe clinical application of commonly used Chinese herbal medicines during pregnancy.

The role of the GABAergic system on insomnia.

Sleep is an essential activity for the survival of mammals. Good sleep quality helps promote the performance of daily functions. In contrast, insufficient sleep reduces the efficiency of daily activities, causes various chronic diseases like Alzheimer's disease, and increases the risk of having accidents. The GABAergic system is the primary inhibitory neurotransmitter system in the central nervous system. It transits the gamma-aminobutyric acid (GABA) neurotransmitter via GABAA and GABAB receptors to counterbalance excitatory neurotransmitters, such as glutamate, noradrenaline, serotonin, acetylcholine, orexin, and dopamine, which release and increase arousal activities during sleep. Several studies emphasized that dysfunction of the GABAergic system is related to insomnia, the most prevalent sleep-related disorder. The GABAergic system comprises the GABA neurotransmitter, GABA receptors, GABA synthesis, and degradation. Many studies have demonstrated that GABA levels correlate with sleep quality, suggesting that modulating the GABAergic system may be a promising therapeutic approach for insomnia. In this article, we highlight the significance of sleep, the classification and pathology of insomnia, and the impact of the GABAergic system changes on sleep. In addition, we also review the medications that target the GABAergic systems for insomnia, including benzodiazepines (BZDs), non-BZDs, barbiturates, GABA supplements, and Chinese herbal medicines.

Neuroprotective effects of methanolic extract from Chuanxiong Rhizoma in mice with middle cerebral artery occlusion-induced ischemic stroke: suppression of astrocyte- and microglia-related inflammatory response.

BACKGROUND: In traditional Asian medicine, dried rhizomes of Ligusticum chuanxiong Hort. (Chuanxiong Rhizoma [CR]) have long been used to treat pain disorders that affect the head and face such as headaches. Furthermore, they have been used primarily for blood circulation improvement or as an analgesic and anti-inflammatory medicine. This study aimed to investigate the neuroprotective effects of a methanol extract of CR (CRex) on ischemic stroke in mice caused by middle cerebral artery occlusion (MCAO). METHODS: C57BL/6 mice were given a 1.5-h transient MCAO (MCAO control and CRex groups); CRex was administered in the mice of the CRex group at 1,000-3,000 mg/kg either once (single dose) or twice (twice dose) before MCAO. The mechanism behind the neuroprotective effects of CRex was examined using the following techniques: brain infarction volume, edema, neurological deficit, novel object recognition test (NORT), forepaw grip strength, and immuno-fluorescence staining. RESULTS: Pretreating the mice with CRex once at 1,000 or 3,000 mg/kg and twice at 1,000 mg/kg 1 h before MCAO, brought about a significantly decrease in the infarction volumes. Furthermore, pretreating mice with CRex once at 3,000 mg/kg 1 h before MCAO significantly suppressed the reduction of forepaw grip strength of MCAO-induced mice. In the MCAO-induced group, preadministration of CRex inhibited the reduction in the discrimination ratio brought on by MCAO in a similar manner. CRex exhibited these effects by suppressing the activation of astrocytes and microglia, which regulated the inflammatory response. CONCLUSIONS: This study proposes a novel development for the treatment of ischemic stroke and provides evidence favoring the use of L. chuanxiong rhizomes against ischemic stroke.

Telomere-to-telomere genome assembly of Oldenlandia diffusa.

We report the complete telomere-to-telomere genome assembly of Oldenlandia diffusa which renowned in traditional Chinese medicine, comprising 16 chromosomes and spanning 499.7 Mb. The assembly showcases 28 telomeres and minimal gaps, with a total of only five. Repeat sequences constitute 46.41% of the genome, and 49,701 potential protein-coding genes have been predicted. Compared with O. corymbosa, O. diffusa exhibits chromosome duplication and fusion events, diverging 20.34 million years ago. Additionally, a total of 11 clusters of terpene synthase have been identified. The comprehensive genome sequence, gene catalog, and terpene synthase clusters of O. diffusa detailed in this study will significantly contribute to advancing research in this species' genetic, genomic, and pharmacological aspects.

Exploring the Therapeutic Effects of Atractylodes macrocephala Koidz against Human Gastric Cancer.

Atractylodes macrocephala Koidz (AMK) is a traditional herbal medicine used for thousands of years in East Asia to improve a variety of illnesses and conditions, including cancers. This study explored the effect of AMK extract on apoptosis and tumor-grafted mice using AGS human gastric adenocarcinoma cells. We investigated the compounds, target genes, and associated diseases of AMK using the Traditional Chinese Medical Systems Pharmacy (TCMSP) database platform. Cell viability assay, cell cycle and mitochondrial depolarization analysis, caspase activity assay, reactive oxygen species (ROS) assay, and wound healing and spheroid formation assay were used to investigate the anti-cancer effects of AMK extract on AGS cells. Also, in vivo studies were conducted using subcutaneous xenografts. AMK extract reduced the viability of AGS cells and increased the sub-G1 cell fraction and the mitochondrial membrane potential. Also, AMK extract increased the production of ROS. AMK extract induced the increased caspase activities and modulated the mitogen-activated protein kinases (MAPK). In addition, AMK extract effectively inhibited AGS cell migration and led to a notable reduction in the growth of AGS spheroids. Moreover, AMK extract hindered the growth of AGS xenograft tumors in NSG mice. Our results suggest that AMK has anti-cancer effects by promoting cell cycle arrest and inhibiting the proliferation of AGS cancer cells and a xenograft model through apoptosis. This study could provide a novel approach to treat gastric cancer.

Anti-Inflammatory, Analgesic, Functional Improvement, and Chondroprotective Effects of Erigeron breviscapus (Vant.) Hand.-Mazz. Extract in Osteoarthritis: An In Vivo and In Vitro Study.

Osteoarthritis (OA) is a degenerative bone disease characterized by inflammation as a primary pathology and currently lacks therapeutic interventions to impede its progression. Erigeron breviscapus (Vant.) Hand.-Mazz. (EB) is an east Asian herbal medicine with a long history of use and a wide range of confirmed efficacy against cardiovascular and central nervous system diseases. The purpose of this study is to evaluate whether EB is worthy of further investigation as a treatment for OA based on anti-inflammatory activity. This study aims to assess the potential of EB as a treatment for OA, focusing on its anti-inflammatory properties. Analgesic effects, functional improvements, and inhibition of cartilage destruction induced by EB were evaluated in acetic acid-induced peripheral pain mice and monosodium iodoacetate-induced OA rat models. Additionally, the anti-inflammatory effect of EB was assessed in serum and cartilage tissue in vivo, as well as in lipopolysaccharide-induced RAW 264.7 cells. EB demonstrated a significant alleviation of pain, functional impairment, and cartilage degradation in OA along with a notable inhibition of pro-inflammatory cytokines, including interleukin-1ß, interleukin-6, matrix metalloproteinases 13, and nitric oxide synthase 2, both in vitro and in vivo, in a dose-dependent manner compared to the active control. Accordingly, EB merits further exploration as a potential disease-modifying drug for OA, capable of mitigating the multifaceted pathology of osteoarthritis through its anti-inflammatory properties. Nonetheless, additional validation through a broader experimental design is essential to substantiate the findings of this study.

Recurrence of sarcoidosis accompanied by lung cancer after drug-induced pulmonary sarcoidosis with lung injury.

Sarcoidosis is a multisystemic granulomatous disease that is frequently localized in the lungs and lymph nodes. We herein report a case of pulmonary sarcoidosis secondary to shin'iseihaito administration. During remission with 5 mg prednisolone/day of maintenance treatment, chest computed tomography revealed a mass in the left lower lobe with re-enlarged bilateral hilar/mediastinal lymph nodes. Transbronchial lung biopsy of the mass and endobronchial ultrasound-guided transbronchial needle aspiration of mediastinal lymph nodes revealed adenocarcinoma and noncaseating granulomas, respectively. Based on these findings, the patient was diagnosed with sarcoidosis recurrence associated with lung cancer without cancer metastasis. We present the case of sarcoidosis recurrence associated with lung cancer after drug-induced pulmonary sarcoidosis with lung injury. To our knowledge, this is the first report of sarcoidosis triggered by drug administration and lung cancer. Histological diagnosis of mediastinal lymphadenopathy with lung cancer is essential for differentiating metastasis from sarcoidosis.

Perception and Use of Herbal Medicine in General Practice Patients: A Cross-Sectional Study in Saudi Arabia.

BACKGROUND: In Saudi Arabia, herbal medicine is an essential component of traditional health practices, reflecting a deep cultural appreciation for natural remedies. Despite widespread use, comprehensive data on perceptions and utilization among general practice patients are scarce. This study aims to elucidate the patterns of herbal medicine use, associated beliefs, and communication with healthcare professionals in this context. METHODS: A cross-sectional survey was conducted using an online questionnaire distributed through social media and professional networks, targeting adult residents of Saudi Arabia. The survey encompassed questions on demographic characteristics, use of herbal medicine, reasons for use, sources of herbal products, perceptions of efficacy and safety, and discussions with healthcare professionals about herbal medicine usage. RESULTS: The survey was completed by 1,184 participants, with 736 (62%) reporting the use of herbal medicines in the past 12 months. Among these users, the age group 30-39 was most represented (328/1,184, 27.8%), while participants over 60 were the least (66/1,184, 5.6%). Herbal medicines were primarily used for general wellness (332/736, 45%) and treatment of specific ailments (221/736, 30%). The majority obtained their herbal medicines from pharmacies (427/736, 58%), and 294 (40% of users) used them as alternatives to prescribed medications. Only 259 (35% of herbal medicine users) had discussed their usage with healthcare professionals. Most users believed in the safety (515/736, 70%) and effectiveness (478/736, 65%) of herbal remedies, with a significant portion (626/736, 85%) advocating for more scientific research. CONCLUSION: This study reveals a significant engagement with and positive perception of herbal medicine among general practice patients in Saudi Arabia, alongside a notable gap in communication between patients and healthcare providers. The findings highlight the need for integrating discussions on herbal medicine into patient care, encouraging evidence-based, safe use through better-informed healthcare practices.