Chian-Jiun Liou

Wen-Chung Huang, Shu-Ju Wu, Xuan-Min Liu, Shu-Chen Cheng, Po-Ting Lin, Chun-Ling Kuo and Chian-Jiun Liou. Biomolecules & Therapeutics 2026;34:676-88. https://doi.org/10.4062/biomolther.2025.162

Mulberroside A is isolated from mulberries (Morus alba L.) and is reported to have anti-inflammatory responses in interleukin-1β–induced chondrocytes. However, the effects of mulberroside A on airway inflammation and airway hyperresponsiveness in asthmatic mice have not been reported. This study explored whether mulberroside A ameliorates airway inflammation and airway hyperresponsiveness in asthmatic mice. We also assessed the anti-inflammatory and antioxidant effects of mulberroside A in tracheal epithelial cells. We conducted a preclinical study using mouse models of induced asthma treated with mulberroside A and a complementary in vitro study using tracheal epithelial cells. Ovalbumin (OVA) or OVA/lipopolysaccharide (LPS)-sensitized female BALB/c mice were treated with an intraperitoneal injection of mulberroside A (10 mg/kg or 20 mg/kg). In the OVA-sensitized mouse model, mulberroside A attenuated airway hyperresponsiveness, inflammatory cell infiltration, and goblet cell hyperplasia in the lungs. Furthermore, it alleviated oxidative stress and airway inflammation by inhibiting Th2-associated cytokine expression. Treatment of inflammatory tracheal epithelial cells with mulberroside A effectively reduced the production of reactive oxygen species, pro-inflammatory cytokines, and eotaxin. Mulberroside A also inhibited monocyte attachment to inflammatory tracheal epithelial cells and reduced the levels of intercellular adhesion molecule-1. In the OVA/LPS-sensitized mouse model, mulberroside A significantly decreased neutrophil infiltration of lung tissue and bronchoalveolar lavage fluid, where it also inhibited some inflammatory cytokines and Th2-related cytokines. Thus, mulberroside A shows potential for improving airway inflammation in asthma.

Trichosanthes kirilowii is a plant used in traditional Chinese medicine. Its fruits, seeds, and roots can all be used medicinally. The fruit of T. kirilowii has a moistening effect on the lung for arresting cough. However, there is no scientific research to prove that the fruit of T. kirilowii can improve asthma. Herein, we evaluated whether T. kirilowii fruit extract (TK) could reduce airway inflammation and airway hyperresponsiveness (AHR) in a murine model of asthma. Female BALB/c mice were sensitized with ovalbumin to induce asthma and treated with varying oral doses of TK from days 14 to 27 of the experiment. Additionally, IL‐4/TNF‐α‐stimulated BEAS‐2B cells were treated with different doses of TK to investigate inflammatory cytokine and chemokine secretion. TK treatment significantly mitigated AHR, eosinophil infiltration, and airway inflammation in the lungs of asthmatic mice. It also alleviated goblet cell hyperplasia and lung ROS levels while modulating Th2‐associated cytokine levels in the bronchoalveolar lavage fluid. Moreover, TK effectively alleviated proinflammatory cytokine, chemokine, and eotaxin in IL‐4 and TNF‐α‐stimulated BEAS‐2B cells. Our results indicate that TK effectively improved asthma symptoms in mice through suppressed Th2‐cell activation, which mitigated airway inflammation, oxidative stress, and AHR.

Gypenoside XIII is isolated from Gynostemma pentaphyllum (Thunb.) Makino. In mice, G. pentaphyllum extract and gypenoside LXXV have been shown to improve non‐alcoholic steatohepatitis (NASH). This study investigated whether gypenoside XIII can regulate lipid accumulation in fatty liver cells or attenuate NASH in mice. We used HepG2 hepatocytes to establish a fatty liver cell model using 0.5 mM oleic acid. Fatty liver cells were treated with different concentrations of gypenoside XIII to evaluate the molecular mechanisms of lipid metabolism. In addition, a methionine/choline‐deficient diet induced NASH in C57BL/6 mice, which were given 10 mg/kg gypenoside XIII by intraperitoneal injection. In fatty liver cells, gypenoside XIII effectively suppressed lipid accumulation and lipid peroxidation. Furthermore, gypenoside XIII significantly increased SIRT1 and AMPK phosphorylation to decrease acetyl‐CoA carboxylase phosphorylation, reducing fatty acid synthesis activity. Gypenoside XIII also decreased lipogenesis by suppressing sterol regulatory element‐binding protein 1c and fatty acid synthase production. Gypenoside XIII also increased lipolysis and fatty acid β‐oxidation by promoting adipose triglyceride lipase and carnitine palmitoyltransferase 1, respectively. In an animal model of NASH, gypenoside XIII effectively decreased the lipid vacuole size and number and reduced liver fibrosis and inflammation. These findings suggest that gypenoside XIII can regulate lipid metabolism in fatty liver cells and improve liver fibrosis in NASH mice. Therefore, gypenoside XIII has potential as a novel agent for the treatment of NASH.

Mulberroside F is isolated from the leaves and roots of Morus alba L. Here, we investigated whether mulberroside F could alleviate airway inflammation and eosinophil infiltration in the lungs of asthmatic mice. We also examined whether mulberroside F attenuated inflammatory responses in human tracheal epithelial BEAS‐2B cells. Female BALB/c mice were sensitized and challenged with ovalbumin (OVA), and administered different doses of mulberroside F via intraperitoneal injection. Additionally, tumor necrosis factor (TNF)‐α‐stimulated BEAS‐2B cells were treated with various doses of mulberroside F, followed by detection of the expressions of inflammatory cytokines and chemokines. The results demonstrated that mulberroside F mitigated the levels of proinflammatory cytokines and chemokines, and CCL11, in inflammatory BEAS‐2B cells. Mulberroside F also suppressed reactive oxygen species (ROS) production and ICAM‐1 expression in TNF‐α‐stimulated BEAS‐2B cells, which effectively suppressed monocyte cell adherence. In an animal model of asthma, mulberroside F treatment attenuated airway hyperresponsiveness, eosinophil infiltration, and goblet cell hyperplasia. Mulberroside F treatment also decreased lung fibrosis and airway inflammation in OVA‐sensitized mice. Moreover, mulberroside F significantly reduced expressions of Th2‐associated cytokines (including interleukin(IL)‐4, IL‐5, and IL‐13) in bronchoalveolar lavage fluid compared to OVA‐sensitized mice. Our results confirmed that mulberroside F is a novel bioactive compound that can effectively reduce airway inflammation and eosinophil infiltration in asthmatic mice via inhibition of Th2‐cell activation.

Our previous study found that oral administration of Gynostemma pentaphyllum extract can attenuate airway hyperresponsiveness (AHR) and reduce eosinophil infiltration in the lungs of asthmatic mice. Gypenoside A is isolated from G. pentaphyllum. In this study, we investigated whether gypenoside A can effectively reduce asthma in mice. Asthma was induced in BALB/c mice by ovalbumin injection. Asthmatic mice were treated with gypenoside A via intraperitoneal injection to assess airway inflammation, AHR, and immunomodulatory effects. In vitro, gypenoside A reduced inflammatory and oxidative responses in inflammatory tracheal epithelial cells. Experimental results showed that gypenoside A treatment can suppress eosinophil infiltration in the lungs, reduce tracheal goblet cell hyperplasia, and attenuate AHR. Gypenoside A significantly reduced Th2 cytokine expression and also inhibited the expression of inflammatory genes and proteins in the lung and bronchoalveolar lavage fluid. In addition, gypenoside A also significantly inhibited the secretion of inflammatory cytokines and chemokines and reduced oxidative expression in inflammatory tracheal epithelial cells. The experimental results suggested that gypenoside A is a natural compound that can effectively reduce airway inflammation and AHR in asthma, mainly by reducing Th2 cell activation.

Airway respiratory distress syndrome (ARDS) is usually caused by a severe pulmonary infection. However, there is currently no effective treatment for ARDS. Traditional Chinese medicine (TCM) has been shown to effectively treat inflammatory lung diseases, but a clear mechanism of action of TCM is not available. Perilla fruit water extract (PFWE) has been used to treat cough, excessive mucus production, and some pulmonary diseases. Thus, we propose that PFWE may be able to reduce lung inflammation and neutrophil infiltration in a lipopolysaccharide (LPS)-stimulated murine model. C57BL/6 mice were stimulated with LPS (10μg/mouse) by intratracheal (IT) injection and treated with three doses of PFWE (2, 5, and 8g/kg) by intraperitoneal (IP) injections. To investigate possible mechanisms, A549 cells were treated with PFWE and stimulated with LPS. Our results showed that PFWE decreased airway resistance, neutrophil infiltration, vessel permeability, and interleukin (IL)-6 and chemokine (C-C motif) ligand 2 (CCL2/MCP-1) expressions in vivo. In addition, the PFWE inhibited the expression of IL-6, CCL2/MCP-1, chemokine (CXC motif) ligand 1 (CXCL1/GROα), and IL-8 in vitro. Moreover, PFWE also inhibited the MAPK/JNK-AP-1/c-Fos signaling pathway in A549 cells. In conclusion, we demonstrated that PFWE attenuated pro-inflammatory cytokine and chemokine levels and downregulated neutrophil recruitment through the MAPK/JNK-AP-1/c-Fos pathway. Thus, PFWE can be a potential drug to assist the treatment of ARDS.

Sophoraflavanone G (SG), isolated from Sophora flavescens, has anti-inflammatory and anti-tumor bioactive properties. We previously showed that SG promotes apoptosis in human breast cancer cells and leukemia cells and reduces the inflammatory response in lipopolysaccharide-stimulated macrophages. We investigated whether SG attenuates airway hyper-responsiveness (AHR) and airway inflammation in asthmatic mice. We also assessed its effects on the anti-inflammatory response in human tracheal epithelial cells. Female BALB/c mice were sensitized with ovalbumin, and asthmatic mice were treated with SG by intraperitoneal injection. We also exposed human bronchial epithelial BEAS-2B cells to different concentrations of SG to evaluate its effects on inflammatory cytokine levels. SG treatment significantly reduced AHR, eosinophil infiltration, goblet cell hyperplasia, and airway inflammation in the lungs of asthmatic mice. In the lungs of ovalbumin-sensitized mice, SG significantly promoted superoxide dismutase and glutathione expression and attenuated malondialdehyde levels. SG also suppressed levels of Th2 cytokines and chemokines in lung and bronchoalveolar lavage samples. In addition, we confirmed that SG decreased pro-inflammatory cytokine, chemokine, and eotaxin expression in inflammatory BEAS-2B cells. Taken together, our data demonstrate that SG shows potential as an immunomodulator that can improve asthma symptoms by decreasing airway-inflammation-related oxidative stress.