Herbs for lochia discharge used among postpartum women in Taiwan.

ETHNOPHARMACOLOGICAL RELEVANCE: In the traditional Taiwanese culture of "postpartum confinement", the term "lochia discharge" is a synonym for assisting postpartum uterine involution. Postpartum women in Taiwan consult traditional Chinese medicine (TCM) pharmacies to obtain various TCM formulations that facilitate lochia discharge. AIM OF THE STUDY: As an ethnopharmacy study, we aimed to conduct field investigations to explore the herbal composition of TCM formulations for lochia discharge provided by TCM pharmacies in Taiwan and to identify the pharmaceutical implications of these TCM formulations. MATERIALS AND METHODS: Through stratified sampling, we collected 98 formulations for postpartum lochia discharge from TCM pharmacies, which used a total of 60 medicinal materials. RESULTS: The most common plant families of the medicinal materials found in Taiwanese lochia discharge formulations were Fabaceae and Lauraceae. Abiding by the TCM theory of nature and flavor, most drugs were warm in nature and sweet in flavor, and predominantly focused on the traditional functions of qi tonifying and blood activating. Correlation and network analyses of the medicinal components of lochia discharge formulations identified 11 core herbs, which, in the order of most to least frequently used, include Angelica sinensis, Ligusticum striatum, Glycyrrhiza uralensis, Zingiber officinale, Prunus persica, Eucommia ulmoides, Leonurus japonicus, Lycium chinense, Hedysarum polybotrys, Rehmannia glutinosa, and Paeonia lactiflora. These 11 herbs formed a total of 136 drug combinations in the 98 formulations, with 2-7 herbs in each combination. In addition, in the center of the network were A. sinensis and L. striatum, which jointly appeared in 92.8% of the formulations analyzed. CONCLUSIONS: To our knowledge, this is the first study to systematically review lochia discharge formulations in Taiwan. The results of this study could provide an important basis for subsequent research in the clinical efficacy of Taiwanese lochia discharge formulations and the pharmacological mechanisms of their herbal components.

An Ethnopharmaceutical Study on the Hypolipidemic Formulae in Taiwan Issued by Traditional Chinese Medicine Pharmacies.

Globally, approximately one-third of ischemic heart diseases are due to hyperlipidemia, which has been shown to cause various metabolic disorders. This study was aimed to disassemble and analyze hypolipidemic formulae sold by traditional Chinese medicine (TCM) pharmacies. Using commonly used statistical parameters in ethnopharmacology, we identified the core drug combination of the hypolipidemic formulae, thereby exploring the strategy by which the Taiwanese people select hypolipidemic drugs. Most important of all, we preserved the inherited knowledge of TCM. We visited 116 TCM pharmacies in Taiwan and collected 91 TCM formulae. The formulae were mainly disassembled by macroscopical identification, and the medicinal materials with a relative frequency of citation (RFC) >0.2 were defined as commonly used medicinal materials. Subsequently, we sorted the information of medicinal materials recorded in the Pharmacopeia, searched for modern pharmacological research on commonly used medicinal materials using PubMed database, and visualized data based on the statistical results. Finally, the core hypolipidemic medicinal materials used in folk medicine were obtained. Of the 91 TCM formulae collected in this study, 80 traditional Chinese medicinal materials were used, belonging to 43 families, predominantly Lamiaceae. Roots were the most commonly used part as a medicinal material. There were 17 commonly used medicinal materials. Based on medicinal records in Pharmacopeia, most flavors and properties were warm and pungent, the majority traditional effects were "tonifying and replenishing" and "blood-regulating." Besides, the targeted diseases searching from modern pharmacological studies were diabetes mellitus and dyslipidemia. The core medicinal materials consisted of Astragalus mongholicus Bunge and Crataegus pinnatifida Bunge, and the core formulae were Bu-Yang-Huan-Wu-Tang and Xie-Fu-Zhu-Yu-Tang. In addition, 7 groups of folk misused medicinal materials were found. Although these TCMs have been used for a long period of time, their hypolipidemic mechanisms remain unclear, and further studies are needed to validate their safety and efficacy.

Ethnobotanical Survey on Bitter Tea in Taiwan.

Ethnopharmacological evidence: In Taiwan, herbal tea is considered a traditional medicine and has been consumed for hundreds of years. In contrast to regular tea, herbal teas are prepared using plants other than the regular tea plant, Camellia sinensis (L.) Kuntze. Bitter tea (kǔ-chá), a series of herbal teas prepared in response to common diseases in Taiwan, is often made from local Taiwanese plants. However, the raw materials and formulations have been kept secret and verbally passed down by store owners across generations without a fixed recipe, and the constituent plant materials have not been disclosed. Aim of the study: The aim was to determine the herbal composition of bitter tea sold in Taiwan, which can facilitate further studies on pharmacological applications and conserve cultural resources. Materials and methods: Interviews were conducted through a semi-structured questionnaire. The surveyed respondents were traditional sellers of traditional herbal tea. The relevant literature was collated for a systematic analysis of the composition, characteristics, and traditional and modern applications of the plant materials used in bitter tea. We also conducted an association analysis of the composition of Taiwanese bitter tea with green herb tea (qing-cao-cha tea), another commonly consumed herbal tea in Taiwan, as well as herbal teas in neighboring areas outside Taiwan. Results: After visiting a total of 59 stores, we identified 32 bitter tea formulations and 73 plant materials. Asteraceae was the most commonly used family, and most stores used whole plants. According to a network analysis of nine plant materials used in high frequency as drug pairs, Tithonia diversifolia and Ajuga nipponensis were found to be the core plant materials used in Taiwanese bitter tea. Conclusion: Plant materials used in Taiwanese bitter tea were distinct, with multiple therapeutic functions. Further research is required to clarify their efficacy and mechanisms.

Corrigendum: An Ethnobotanical Study of Medicinal Plants in Kinmen.

[This corrects the article DOI: 10.3389/fphar.2021.681190.].

Ethnobotanical Survey on Skin Whitening Prescriptions of Traditional Chinese Medicine in Taiwan.

The increasing interest and demand for skin whitening products globally, particularly in Asia, have necessitated rapid advances in research on skin whitening products used in traditional Chinese medicine (TCM). Herein, we investigated 74 skin whitening prescriptions sold in TCM pharmacies in Taiwan. Commonly used medicinal materials were defined as those with a relative frequency of citation (RFC) > 0.2 and their characteristics were evaluated. Correlation analysis of commonly used medicinal materials was carried out to identify the core component of the medicinal materials. Of the purchased 74 skin whitening prescriptions, 36 were oral prescriptions, 37 were external prescriptions, and one prescription could be used as an oral or external prescription. After analysis, 90 traditional Chinese medicinal materials were obtained. The Apiaceae (10%; 13%) and Leguminosae (9%; 11%) were the main sources of oral and external medicinal materials, respectively. Oral skin whitening prescriptions were found to be mostly warm (46%) and sweet (53%), while external skin whitening prescriptions included cold (43%) and bitter (29%) medicinal materials. Additionally, mainly tonifying and replenishing effects of the materials were noted. Pharmacological analysis indicated that these medicinal materials may promote wound healing, treat inflammatory skin diseases, or anti-hyperpigmentation. According to the Spearman correlation analysis on interactions among medicinal materials with an RFC > 0.2 in the oral skin whitening prescriptions, Paeonia lactiflora Pall. (white) and Atractylodes macrocephala Koidz. showed the highest correlation (confidence score = 0.93), followed by Ziziphus jujuba Mill. (red) and Astragalus propinquus Schischkin (confidence score = 0.91). Seven medicinal materials in external skin whitening prescriptions with an RFC > 0.2, were classified as Taiwan qi bái sàn (an herbal preparation), including Angelica dahurica (Hoffm.) Benth. & Hook. f. ex Franch. & Sav., Wolfiporia extensa (Peck) Ginns, Bletilla striata (Thunb.) Rchb. f., Atractylodes macrocephala Koidz., Ampelopsis japonica (Thunb.) Makino, Paeonia lactiflora Pall. (white), and Bombyx mori Linnaeus. Skin whitening prescriptions included multiple traditional Chinese medicinal materials. Despite the long history of use, there is a lack of studies concerning skin whitening products, possibly due to the complex composition of traditional Chinese medicine. Further studies are required to assess the efficacy and safety of these traditional Chinese medicinal materials for inclusion in effective, safe, and functional pharmacological products.

Sanghuangporus sanghuang Mycelium Prevents Paracetamol-Induced Hepatotoxicity through Regulating the MAPK/NF-κB, Keap1/Nrf2/HO-1, TLR4/PI3K/Akt, and CaMKKß/LKB1/AMPK Pathways and Suppressing Oxidative Stress and Inflammation.

Liver damage induced by paracetamol overdose is the main cause of acute liver failure worldwide. In order to study the hepatoprotective effect of Sanghuangporus sanghuang mycelium (SS) on paracetamol-induced liver injury, SS was administered orally every day for 6 days in mice before paracetamol treatment. SS decreased serum aminotransferase activities and the lipid profiles, protecting against paracetamol hepatotoxicity in mice. Furthermore, SS inhibited the lipid peroxidation marker malondialdehyde (MDA), hepatic cytochrome P450 2E1 (CYP2E1), and the histopathological changes in the liver and decreased inflammatory activity by inhibiting the production of proinflammatory cytokines in paracetamol-induced acute liver failure. Moreover, SS improved the levels of glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase in the liver. Significantly, SS diminished mitogen-activated protein kinase (MAPK), Toll-like receptor 4 (TLR4), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and the nuclear factor-kappa B (NF-κB) axis, as well as upregulated the Kelch-like ECH-associated protein 1 (Keap1)/erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway, in paracetamol-induced mice. SS mainly inhibited the phosphorylation of the liver kinase B1 (LKB1), Ca2+/calmodulin-dependent kinase kinase ß (CaMKKß), and AMP-activated protein kinase (AMPK) protein expression. Furthermore, the protective effects of SS on paracetamol-induced hepatotoxicity were abolished by compound C, an AMPK inhibitor. In summary, we provide novel molecular evidence that SS protects liver cells from paracetamol-induced hepatotoxicity by inhibiting oxidative stress and inflammation.

Ethnopharmacological Survey of Traditional Chinese Medicine Pharmacy Prescriptions for Dysmenorrhea.

Chinese herbal medicines have long been used for the treatment of dysmenorrhea. The treatment experiences of traditional Chinese medicine (TCM) pharmacies passed down through generations have contributed to a wealth of prescriptions for dysmenorrhea that have achieved significant therapeutic effects in countless Taiwanese women. Therefore, surveying and analyzing these prescriptions may enable us to elucidate the core medication combinations used in TCM prescriptions for dysmenorrhea. In the present study, a field investigation was conducted on various TCM pharmacies in Taiwan. A total of 96 TCM pharmacies were sampled, and 99 prescriptions for dysmenorrhea containing 77 different medicinal materials were collected. Compositae (8%) was the most common botanical source of the medicinal materials, and the predominant TCM property and flavor of the materials were warm (45%) and sweet (73%), respectively. The blood-activating and stasis-dispelling effect (23%) and the qi-tonifying effect (23%) were the most prevalent traditional effects, and the modern pharmacological effects most commonly found in the materials were anti-inflammatory (73%), antitumor (59%), and analgesic (12%) effects. Network analysis of the 77 medicinal materials used in the prescriptions, which was performed using the Traditional Chinese Medicine Inheritance Support System, yielded seven core medicinal materials and the corresponding network diagram. The seven core medicinal materials ranked in order of relative frequency of citation (RFC) were Angelica sinensis (Oliv.) Diels (Dang Gui), Ligusticum chuanxiong Hort (Chuan Qiong), Rehmannia glutinosa Libosch (Di Huang), Paeonia lactiflora Pall (Bai Shao), Hedysarum polybotrys Hand.-Mazz (Hong Qi), Lycium chinense Mill (Gou Qi Zi), and Cinnamomum cassia (L.). J. Presl (Gui Zhi). A total of 58 combinations, each consisting of two to five of the seven medicinal materials and 107 association rules among the materials, were identified. This study provides a record of valuable knowledge on TCM pharmacy prescriptions for dysmenorrhea. The rich medicinal knowledge of TCM pharmacies in Taiwan is worthy of further exploration, and the results of this study can serve as a basis for future pharmacological research and the development of naturally derived medications for dysmenorrhea.

An Ethnobotanical Study of Medicinal Plants in Kinmen.

Kinmen is an outlying island that has the richest plant resources in Taiwan. The objective of this study was to record the methods that people in Kinmen use medicinal plants and to analyze the cultural characteristics of their use. Field investigations were carried out in various towns and villages in Kinmen, and 80 respondents were included in the survey. The search for respondents was conducted through local elderly people and medicinal plant groups. Semi-structured interviews were conducted with the local people to obtain their knowledge of medicinal plants and how they disseminate this information. Informed consent was obtained prior to the interviews, and the following was determined: plant use value (UV), frequency of citation (FC), and factor of informant consensus (Fic). These parameters were used to quantify the data and measure the agreement among the respondents on using plants to treat different diseases. Finally, the survey results were compared with the representative ethnobotanical literature in neighboring areas to evaluate the similarity between plant usage in Kinmen and neighboring areas as well as to determine whether there are new species or novel usages in the study area. In the Kinmen area, phytotherapy is generally used by elderly people with low educational attainments. According to the survey results, 83 medicinal plants belonging to 48 families were collected. These medicinal plants were mainly distributed in the Compositae, Lamiaceae, and Solanaceae families. Eighteen novel uses that have not been previously documented were found, four of which were related to newly recorded medicinal plant species in the Kinmen area. The results showed that 93.98 and 65.06% of the species collected in the present study were also recorded in literature from Taiwan and Fujian, respectively. This study showed that Kinmen's ethnobotanical knowledge is closely related to the Catalogue of Medicinal Plant Resources in Taiwan, and local people indeed shared similar uses of medicinal species with people in Taiwan and Fujian (46.99%). The results from this study highlighted the importance of traditional medicine in the Kinmen area, where people have a specific understanding of using medicinal plants and communication with people in Taiwan and Fujian Province in China. It was found that Kinmen shares ethnobotanical knowledge with Taiwan and Fujian.

An Ethnobotanical Study on Qing-Cao-Chá Tea in Taiwan.

Herbal tea, a beverage prepared from a variety of plant materials excluding the leaves of the tea plant Camellia sinensis (L.) Kuntze of the family Theaceae, for a long time, has been consumed by most Chinese people for preventive and/or therapeutic health care. Usually, it is brewed or prepared as a decoction of local plants in water. The qing-cao-chá tea, a commercial herbal tea, is the most common among many differently formulated herbal teas in Taiwan. For hundreds of years, qing-cao-chá tea has played an important role in the prevention and treatment of diseases associated with the environmental conditions in Taiwan. However, research studies in this field have been insufficient. The raw material formulas of qing-cao-chá tea have always been passed down from "masters" to "apprentices." Hence, there is no systematic collation or record, and, therefore, there is a need to assess and confirm the composition, safety, and effectiveness of the raw materials. This study aimed to document the uses of Taiwan's qing-cao-chá tea through a semi-structured interview survey and investigate the background of traditional practitioners, tea compositions, and plant origins and uses. This will improve our understanding of the knowledge inherited by the practitioners and the theoretical basis of the medicinal uses of these teas. In our field investigation, we visited 86 shops and assessed 71 raw ingredients of qing-cao-chá tea. A semi-structured questionnaire was used to conduct the interviews. During the interviews, in addition to written records, audio and video recordings were made, and photographs were taken with the permission of the interviewees. The qing-cao-chá raw materials have long been used as herbal teas, although more research should clarify their efficacy and safety. Traditional sellers of qing-cao-chá tea were mainly males, and most shops have been in operation for more than 71 years. Some of the raw materials were derived from multiple sources, including different plants, and were often mixed without any safety concerns. To our knowledge, this is the first systematic ethnobotanical study on qing-cao-chá tea that assesses and confirms its herbal ingredients. Our study represents a reference for herbal teas in Taiwan that can be used by the public and regulatory agencies.

Cordyceps cicadae Mycelia Ameliorate Cisplatin-Induced Acute Kidney Injury by Suppressing the TLR4/NF-κB/MAPK and Activating the HO-1/Nrf2 and Sirt-1/AMPK Pathways in Mice.

Acute kidney injury (AKI) is a common clinical problem, characterized by a sudden loss of renal function, a high risk of death, and the eventual development of renal fibrosis and renal failure. Cordyceps cicadae is a traditional Chinese medicine with the potential function of kidney protection. We analyze two sputum extracts, a water extract (WCC), and an ethanol extract (ECC), to assess the potential of treating AKI in an animal model of kidney injury induced by cisplatin. A nephrotoxic mouse model was first established by intraperitoneal injection of cisplatin. Subsequently, WCC and ECC were orally administered in these mice. The results show that WCC and ECC significantly alleviated cisplatin-induced AKI renal histological changes, serum creatinine (CRE) and blood urea nitrogen (BUN) production, and the levels of NO, TNF-α, IL-1ß, and IL-6. The levels of malondialdehyde (MDA) and glutathione (GSH) were suppressed by administration of WCC and ECC. However, WCC treatment prevented these changes significantly better than ECC treatment. In addition, Western blot data showed that WCC attenuated the cisplatin-induced protein expression of cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS), as well as inhibiting nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) activation in the kidney tissues. Furthermore, WCC greatly inhibited the expression of Toll-like receptor 4 (TLR4) and cisplatin-induced NF-κB activation, as well as dramatically increasing the production of antioxidative enzymes (i.e., superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1)), silent information regulator T1 (Sirt1), and p-AMP-activated protein kinase (AMPK) in the kidney tissues. In addition, we found that WCC increased the expression levels of the autophagy-related proteins LC3B and Beclin-1; proapoptotic proteins, including cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP) 1; and organic anion transporters 1 (OAT1) and 3 (OAT3) in the kidney tissues. Finally, WCC, ECC, and two bioactive compounds-adenosine and N6-(2-hydroxyethyl) adenosine (HEA)-inhibited the production of nitrite oxide (NO) and intracellular reactive oxygen species (ROS) triggered by lipopolysaccharide- (LPS-) stimulated RAW264.7 macrophages in vitro. Collectively, WCC could provide a potential therapeutic candidate for the prevention of cisplatin-induced kidney injury through the inhibition of oxidative stress and inflammation.

Ethnobotanical Survey of Natural Galactagogues Prescribed in Traditional Chinese Medicine Pharmacies in Taiwan.

Natural medicinal materials have been used to promote breast milk secretion. Here, we investigated the natural medicinal materials prescribed in traditional Chinese medicine (TCM) pharmacies across Taiwan to induce lactation. We collected medicinal materials from 87 TCM pharmacies, identified them in the prescriptions, and analyzed their drug contents. We examined their botanical origins, biological classifications, traditional usage, and modern pharmacological properties. We used the TCM Inheritance Support System to identify core medicinal materials in galactogenous prescriptions. We collected 81 medicinal materials from 90 galactogenous prescriptions. Leguminosae accounted for 12%, whereas Apiaceae accounted for 7% of all materials examined. The primary medicinal plant parts used were roots and seeds. Nineteen frequently used medicinal materials had a relative frequency of citation of greater than or equal to 0.2. According to their efficacy, 58% were warm, 54% were sweet, and 63% were tonifying; 74% of the frequently used medicinal materials have been showed efficacy against breast cancer. The primary core medicinal material was Angelica sinensis (Oliv.) Diels, whereas the secondary core medicinal materials were Tetrapanax papyrifer (Hook.) K. Koch and Hedysarum polybotrys Hand.-Mazz. Most galactogenous prescriptions consisted of multiple materials from Leguminosae and Apiaceae. The mechanisms underlying galactogenous efficacy warrant further investigations.

Gallic Acid Ameliorated Impaired Lipid Homeostasis in a Mouse Model of High-Fat Diet-and Streptozotocin-Induced NAFLD and Diabetes through Improvement of ß-oxidation and Ketogenesis.

Gallic acid (GA) is a simple polyphenol found in food and traditional Chinese medicine. Here, we determined the effects of GA administration in a combined mouse model of high-fat diet (HFD)-induced obesity and low-dose streptozotocin (STZ)-induced hyperglycemia, which mimics the concurrent non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes pathological condition. By combining the results of physiological assessments, pathological examinations, metabolomic studies of blood, urine, liver, and muscle, and measurements of gene expression, we attempted to elucidate the efficacy of GA and the underlying mechanism of action of GA in hyperglycemic and dyslipidemic mice. HFD and STZ induced severe diabetes, NAFLD, and other metabolic disorders in mice. However, the results of liver histopathology and serum biochemical examinations indicated that daily GA treatment alleviated the high blood glucose levels in the mice and decelerated the progression of NAFLD. In addition, our results show that the hepatoprotective effect of GA in diabetic mice occurs in part through a partially preventing disordered metabolic pathway related to glucose, lipids, amino acids, purines, and pyrimidines. Specifically, the mechanism responsible for alleviation of lipid accumulation is related to the upregulation of ß-oxidation and ketogenesis. These findings indicate that GA alleviates metabolic diseases through novel mechanisms.

Four New Iridoid Metabolites Have Been Isolated from the Stems of Neonauclea reticulata (Havil.) Merr. with Anti-Inflammatory Activities on LPS-Induced RAW264.7 Cells.

One new iridoid, namely neonanin C (1) one monocyclic iridoid ring-opened derivative namely neonanin D (2), two new bis-iridoid derivatives namely reticunin A (3) and reticunin B (4) with sixteen known compounds (5-20) were isolated from the stems of Neonauclea reticulata (Havil.) Merr. These new structures were determined by the detailed analysis of spectroscopic data and comparison with the data of known analogues. Compounds 1-20 were evaluated for inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages cell line. The results showed that all compounds exhibited no obvious cytotoxicity compared to the control group and five compounds including isoboonein (7), syringaresinol (10), (+)-medioresinol (12), protocatechuic acid (14) and trans-caffeic acid (15) exhibited inhibitory activities with IC50 values at 86.27 ± 3.45; 9.18 ± 1.90; 76.18 ± 2.42; 72.91 ± 4.97 and 95.16 ± 1.20 µg/mL, respectively.

Hepatoprotective Effect of Ugonin M, A Helminthostachyszeylanica Constituent, on Acetaminophen-Induced Acute Liver Injury in Mice.

The present study aimed to discover the possible effectiveness of Ugonin M, a unique flavonoid isolated from Helminthostachys zeylanica-a traditional Chinese medicine used as anti-inflammatory medicine-and to elucidate the potential mechanisms of Ugonin M in the acute liver injury induced by acetaminophen (APAP). In this study, Ugonin M significantly ameliorated APAP-induced histopathological changes and the typical liver function biomarkers (i.e., alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (T-Bil)). It also affected APAP-induced abnormal lipid metabolism including total cholesterol (TC) and triglyceride (TG) in the serum. In inflammatory pharmacological action, Ugonin M suppressed the pro-inflammatory mediators such as nitric oxide (NO) and the lipid peroxidation indicator malondialdehyde (MDA). In addition, Ugonin M reinforced hemeoxygenase-1 (HO-1) protein expression and the production of antioxidant enzymes viz superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT). Furthermore, inflammation-associated cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1ß as well as proteins such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were decreased by the pretreatment of Ugonin M. Moreover, this study found that pretreatment of Ugonin M apparently decreased nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) activation via inhibition of the degradation of NF-κB, inhibitory κB-α (IκB-α), extracellular regulated kinase (ERK), c-Jun-N-terminal (JNK), and p38 active phosphorylation. In conclusion, Ugonin M significantly showed a protective effect against APAP-induced liver injury by reducing oxidative stress and inflammation. Thus, Ugonin M could be one of the effective components of H. zeylanica that plays a major role in the treatment of inflammatory disorders.

Preventive Effects of Velvet Antler (Cervus elaphus) against Lipopolysaccharide-Induced Acute Lung Injury in Mice by Inhibiting MAPK/NF-κB Activation and Inducing AMPK/Nrf2 Pathways.

Velvet antler (Cervus elaphus) is a typical traditional animal medicine. It is considered to have various pharmacological effects including stimulation of the immune system, increase in the physical strength, and enhancement of sexual function. This paper aims to investigate the aqueous extract of velvet antler (AVA) in the mouse models of LPS-induced ALI. Inhibition of NO, TNF-α, IL-1ß, IL-6, and IL-10 productions contributes to the attenuation of LPS-induced lung inflammation by AVA. A 5-day pretreatment of AVA prevented histological alterations and enhanced antioxidant enzyme activity in lung tissues. AVA significantly reduced the material (total number of cells and proteins) in the BALF. Western blot analysis revealed that the expression of iNOS and COX-2 and phosphorylation of IκB-α and MAPKs proteins are blocked in LPS-stimulated macrophages as well as LPS-induced lung injury in mice. Consistent with this concept, the phosphorylation of CaMKKß, LKB1, AMPK, Nrf2, and HO-1 was activated after AVA treatment. The results from this study indicate AVA has anti-inflammatory effects in vivo and AVA is a potential model for the development of health food. In addition, its pathways may be at least partially associated with inhibiting MAPK/NF-κB activation and upregulating AMPK/Nrf2 pathways and the regulation of antioxidant enzyme activity.

Alpinumisoflavone attenuates lipopolysaccharide-induced acute lung injury by regulating the effects of anti-oxidation and anti-inflammation both in vitro and in vivo.

Alpinumisoflavone (AIF) is a plant-derived pyranoisoflavone that exhibits a number of pharmacological activities, but the protective effects of AIF against pulmonary inflammation are still unknown. This study aimed to investigate the anti-inflammatory effects and possible molecular mechanisms of AIF in both lipopolysaccharide (LPS)-stimulated macrophages and mice. The results revealed that AIF dramatically suppressed the production of pro-inflammatory mediators [including tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1ß, IL-17, intercellular adhesion molecule-1 (ICAM-1), and nitric oxide (NO)] and increased the levels of anti-oxidative enzymes [including catalase (CAT), heme oxygenase-1 (HO-1), glutathione peroxidase (GPx), and superoxide dismutase (SOD)] both in vitro and in vivo. Additionally, pre-treatment with AIF could not only significantly prevent histopathological changes and neutrophil infiltration but also decreased the expression levels of nuclear factor-kappa B (NF-κB), mitogen-activated protein kinases (MAPKs), and the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome, as well as IL-17 production in LPS-induced lung tissues. The anti-inflammatory effects of AIF were mediated by up-regulating anti-oxidative enzymes and suppressing the NF-κB, MAPK, NLRP3 inflammasome and IL-17 signaling pathways. This is the first study to reveal that AIF has a protective effect against LPS-induced lung injury in mice.

3, 4-dihydroxybenzalacetone attenuates lipopolysaccharide-induced inflammation in acute lung injury via down-regulation of MMP-2 and MMP-9 activities through suppressing ROS-mediated MAPK and PI3K/AKT signaling pathways.

3, 4-Dihydroxybenzalacetone (DBL) is a constituent of Phellinus linteus. This study demonstrated the protective effect of DBL on lipopolysaccharide (LPS)-induced acute lung injuries in mice. Pretreatment with DBL significantly improved LPS-induced histological alterations in lung tissues. In addition, DBL markedly reduced the total cell number, the leukocytes, the protein concentrations, and decreased the release of nitrite, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 and the activities of matrix metalloproteinase (MMP)-2 and -9 in the bronchoalveolar lavage fluid. DBL also inhibited the W/D ratio and myeloperoxidase activity in the lung tissues. Western blot analysis indicated DBL efficiently blocked the protein expressions of inducible nitric oxide synthase, cyclooxygenase-2, MMP-2, MMP-9, and the phosphorylation of mitogen-activated protein kinase (MAPK), phosphoinositide-3-kinase (PI3K), AKT, Toll-like receptor 4 (TLR4) and nuclear factor (NF)-κB. Moreover, DBL enhanced the expression of anti-oxidant proteins, such as superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx). Based on our results, DBL might be a potential target for attenuating tissue oxidative injuries and nonspecific pulmonary inflammation.

Protective Effects of Tormentic Acid, a Major Component of Suspension Cultures of Eriobotrya japonica Cells, on Acetaminophen-Induced Hepatotoxicity in Mice.

An acetaminophen (APAP) overdose can cause hepatotoxicity and lead to fatal liver damage. The hepatoprotective effects of tormentic acid (TA) on acetaminophen (APAP)-induced liver damage were investigated in mice. TA was intraperitoneally (i.p.) administered for six days prior to APAP administration. Pretreatment with TA prevented the elevation of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (T-Bil), total cholesterol (TC), triacylglycerol (TG), and liver lipid peroxide levels in APAP-treated mice and markedly reduced APAP-induced histological alterations in liver tissues. Additionally, TA attenuated the APAP-induced production of nitric oxide (NO), reactive oxygen species (ROS), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß), and IL-6. Furthermore, the Western blot analysis showed that TA blocked the protein expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), as well as the inhibition of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) activation in APAP-injured liver tissues. TA also retained the superoxidase dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) in the liver. These results suggest that the hepatoprotective effects of TA may be related to its anti-inflammatory effect by decreasing thiobarbituric acid reactive substances (TBARS), iNOS, COX-2, TNF-α, IL-1ß, and IL-6, and inhibiting NF-κB and MAPK activation. Antioxidative properties were also observed, as shown by heme oxygenase-1 (HO-1) induction in the liver, and decreases in lipid peroxides and ROS. Therefore, TA may be a potential therapeutic candidate for the prevention of APAP-induced liver injury by inhibiting oxidative stress and inflammation.

Ugonin M, a Helminthostachys zeylanica Constituent, Prevents LPS-Induced Acute Lung Injury through TLR4-Mediated MAPK and NF-κB Signaling Pathways.

Helminthostachys zeylanica (L.) Hook. is plant that has been used in traditional Chinese medicine for centuries for the treatment of inflammation, fever, pneumonia, and various disorders. The aims of the present study are to figure out the possible effectiveness of the component Ugonin M, a unique flavonoid isolated from H. zeylanica, and to elucidate the mechanism(s) by which it works in the LPS-induced ALI model. In this study, Ugonin M not only inhibited the production of pro-inflammatory mediators such as NO, TNF-α, IL-1ß, and IL-6, as well as infiltrated cellular counts and protein content in the bronchoalveolar lavage fluid (BALF) of lipopolysaccharides (LPS)-induced acute lung injury (ALI) mice, but also ameliorated the severity of pulmonary edemas through the score of a histological examination and the ratio of wet to dry weight of lung. Moreover, Ugonin M was observed to significantly suppress LPS-stimulated protein levels of iNOS and COX-2. In addition, we found that Ugonin M not only obviously suppressed NF-κB and MAPK activation via the degradation of NF-κB and IκB-α as well as ERK and p38MAPK active phosphorylation but also inhibited the protein expression level of TLR4. Further, Ugonin M treatment also suppressed the protein levels of MPO and enhanced the protein expressions of HO-1 and antioxidant enzymes (SOD, GPx, and CAT) in lung tissue of LPS-induced ALI mice. It is anticipated that through our findings, there is strong evidence that Ugonin M may exert a potential effect against LPS-induced ALI mice. Hence, Ugonin M could be one of the major effective components of H. zeylanica in the treatment of inflammatory disorders.

Anti-Inflammatory Activity of Sanghuangporus sanghuang Mycelium.

Acute lung injury (ALI) is characterized by inflammation of the lung tissue and oxidative injury caused by excessive accumulation of reactive oxygen species. Studies have suggested that anti-inflammatory or antioxidant agents could be used for the treatment of ALI with a good outcome. Therefore, our study aimed to test whether the mycelium extract of Sanghuangporus sanghuang (SS-1), believed to exhibit antioxidant and anti-inflammatory properties, could be used against the excessive inflammatory response associated with lipopolysaccharides (LPS)-induced ALI in mice and to investigate its possible mechanism of action. The experimental results showed that the administration of SS-1 could inhibit LPS-induced inflammation. SS-1 could reduce the number of inflammatory cells, inhibit myeloperoxidase (MPO) activity, regulate the TLR4/PI3K/Akt/mTOR pathway and the signal transduction of NF-κB and MAPK pathways in the lung tissue, and inhibit high mobility group box-1 protein 1 (HNGB1) activity in BALF. In addition, SS-1 could affect the synthesis of antioxidant enzymes Heme oxygenase 1 (HO-1) and Thioredoxin-1 (Trx-1) in the lung tissue and regulate signal transduction in the KRAB-associated protein-1 (KAP1)/nuclear factor erythroid-2-related factor Nrf2/Kelch Like ECH associated Protein 1 (Keap1) pathway. Histological results showed that administration of SS-1 prior to induction could inhibit the large-scale LPS-induced neutrophil infiltration of the lung tissue. Therefore, based on all experimental results, we propose that SS-1 exhibits a protective effect against LPS-induced ALI in mice. The mycelium of S. sanghuang can potentially be used for the treatment or prevention of inflammation-related diseases.