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Lonicera japonica Thunb. (LJT) is known for its valuable medicinal properties that highlight its potential application in the pharmaceutical and health food industry. We predict that LJT polyphenols by network pharmacology may be involved in immunomodulation, and the study of LJT polyphenols regulating immunity is still insufficient; therefore, we experimentally found that LJT enhances immunity by promoting the proliferation and phagocytic activity of RAW246.7 cells. A model of an immunosuppressed mouse was constructed using cyclophosphamide-induced, and LJT was extracted for the intervention. We found that LJT restored immune homeostasis in immune deficiency mice by inhibiting the abnormal apoptosis in lymphocytes, enhancing natural killer cell cytotoxicity, promoting T lymphocyte proliferation, and increasing the CD4 + and CD8 + T lymphocytes in quantity. Moreover, LJT treatment modulates immunity by significantly downregulating lipopolysaccharide-induced inflammation and oxidative stress levels. We verified the immunomodulatory function of LJT through both cell and animal experiments. The combination of potential-protein interactions and molecular docking later revealed that LJT polyphenols were associated with immunomodulatory effects on MAPK1; together, LJT intervention significantly modulates the immune, with the activation of MAPK1 as the underlying mechanism of action, which provided evidence for the utilization of LJT as a nutraceutical in immune function., (© 2024 Institute of Food Technologists.)

Lonicera japonica Thunb [...].

Background: Lonicera japonica Thunb is a common herb in East Asia. The flower buds are usually regarded as the traditional medicinal part, while leaves and stems are considered less valuable and receive little attention. This study compared the chemical constituents and anti-inflammatory effects of the different tissues in L. japonica Thunb for the first time., Results: Thirty compounds were identified by ultra-performance liquid chromatography-photodiode detector-quadrupole / time of flight-mass spectrometry (UPLC-PDA-Q/TOF-MS/MS) analysis. Hydroxycinnamic acids, flavonoids, and iridoids were identified as the major components. The flower buds (FLJ), leaves (LLJ), and stems (SLJ) of L. japonica Thunb showed strong similarities in chemical components. The LLJ contained higher levels of hydroxycinnamic acids and flavonoids than the FLJ and SLJ. Furthermore, FLJ, LLJ, and SLJ exhibited potent anti-inflammatory activity in croton oil-induced ear edema and carrageenan-induced paw edema assays in mice. Moreover, FLJ, LLJ, and SLJ showed a cytoprotective effect on lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophages. Lipopolysaccharide-induced increases in nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) were suppressed by treatments of FLJ, LLJ, and SLJ, respectively. The LLJ possessed a stronger anti-inflammatory effect than the FLJ., Conclusion: Leaves and stems of L. japonica Thunb have chemical components and anti-inflammatory properties similar to flower buds, and may become alternative or supplementary sources of flower buds. © 2019 Society of Chemical Industry., (© 2019 Society of Chemical Industry.)

Objectives: The water extracts of Cinnamomum cassia Blume bark (CCB; Lauraceae), Lonicera japonica Thunb. flower (LJT; Caprifoliaceae), and Agrimonia pilosa Ledeb. leaves (APL; Rosaceae) prevented amyloid-β (25-35)-induced cell death in PC12 cells in our preliminary study. We evaluated whether long-term oral consumption of CCB, LJT, and APL improves cognitive dysfunction and glucose homeostasis in rats with experimentally induced AD-type dementia., Methods: Male rats received hippocampal CA1 infusions of amyloid-β (25-35, AD) or amyloid-β (35-25, non-plaque forming, normal-controls, Non-AD-CON), at a rate of 3.6 nmol/day for 14 days. AD rats were divided into four groups receiving either 2% lyophilized water extracts of CCB, LJT, or APL or 2% dextrin (AD-CON) in high-fat diets (43% energy as fat)., Results: Hippocampal amyloid-β deposition, tau phosphorylation, and expressions of tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS) (neruoinflammation markers) were increased, and insulin signaling decreased in AD-CON. CCB, LJT, and APL all prevented hippocampal amyloid-β accumulation and enhanced hippocampal insulin signaling. CCB, LJT, and APL decreased TNF-α and iNOS in the hippocampus and especially APL exhibited the greatest decrease. AD-CON exhibited cognitive dysfunction in passive avoidance and water maze tests, whereas CCB, LJT, and APL protected against cognitive dysfunction, and APL was most effective and was similar to Non-AD-CON. AD-CON had less fat oxidation as an energy fuel, but it was reversed by CCB, LJT, and especially APL. APL-treated rats had less visceral fat than AD-CON rats. AD-CON rats exhibited impaired insulin sensitivity and increased insulin secretion during oral glucose tolerance test compared with Non-AD-CON, but CCB and APL prevented the impairment., Discussion: These results supported that APL, LJT, and CCB effectively prevent the cognitive dysfunction and the impairment of energy and glucose homeostasis induced by amyloid-β deposition by reducing neuroinflammation and enhancing insulin signaling. APL exhibited the greatest effectiveness for improving cognitive function.

Nonalcoholic steatohepatitis (NASH) is characterized as fat accumulation in the hepatic tissue associated with various degrees of inflammation and progressive fibrosis. The potent anti-inflammatory and ethnopharmacological properties of Lonicera japonica Thunb. (Caprifoliaceae) make it an excellent source of novel medicinal targets for the treatment of NASH. The aim of the study was to investigate the effects of L. japonica ethanol extract (LJEE) on NASH in mice. C57BL/6J mice were fed with methionine-choline-deficient diet (MCDD) for eight weeks to promote the development of NASH. After development of the model, the mice were administered LJEE once daily via oral gavage at doses of 100, 200, or 300 mg/kg for another four weeks. Simultaneous treatments with LJEE (300 mg/kg/day) resulted in pronounced improvements in liver steatosis, ballooning degeneration, and inflammation. LJEE prevented MCDD-induced plasma level increases in aspartate aminotransferase and alanine aminotransferase. LJEE significantly reduced hepatic malondialdehyde level and ameliorated hepatic inflammation and fibrosis in MCDD-fed mice, which were associated with down-regulation of cytochrome P450 2E1 suppression of multiple proinflammatory and profibrotic genes. LJEE can prevent hepatic steatosis by reducing hepatic peroxisome acyl-CoA:diacylglycerol acyltransferase 2 expression, as well as by inducing proliferator-activated receptor α expression. In addition, the LJEE treatments caused significant reduction in the phosphorylated form of Jun N-terminal kinase along with an increase in the phosphorylated level of extra cellular signal-regulated kinase 1/2. Our study demonstrated the protective role of LJEE in ameliorating nutritional steatohepatitis.

Lonicera japonica Thunb. (Caprifoliaceae) is a traditional herbal medicine and has been used to treat diabetic symptoms. Notwithstanding its use, the scientific basis on anti-diabetic properties of L. japonica is not yet established. This study is designed to investigate anti-diabetic effects of L. japonica in type 2 diabetic rats. L. japonica was orally administered at the dose of 100 mg/kg in high-fat diet-fed and low-dose streptozotocin-induced rats. After the treatment of 4 weeks, L. japonica reduced high blood glucose level and homeostatic model assessment of insulin resistance in diabetic rats. In addition, body weight and food intake were restored by the L. japonica treatment. In the histopathologic examination, the amelioration of damaged β-islet in pancreas was observed in L. japonica-treated diabetic rats. The administration of L. japonica elevated peroxisome proliferator-activated receptor gamma and insulin receptor subunit-1 protein expressions. The results demonstrated that L. japonica had anti-diabetic effects in type 2 diabetic rats via the peroxisome proliferator-activated receptor gamma regulatory action of L. japonica as a potential mechanism., (Copyright © 2015 John Wiley & Sons, Ltd.)

In the current study, we evaluated the anti-inflammatory effects of Lonicera japonica THUNB. (LJ) and its underlying molecular mechanism in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. Our results indicated that LJ significantly inhibits LPS-stimulated production of nitric oxide (NO) and prostaglandin E2 (PGE2). In addition, LJ inhibited inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at both the protein and mRNA levels. In LPS-stimulated BV-2 microglial cells, LJ inhibited proinflammatory cytokines and chemokines, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9) enzymatic activities, and/or mRNA expression, as well as reactive oxygen species (ROS) production. LJ significantly suppressed activation of nuclear factor-κB (NF-κB) and its translocation from the cytosol to the nucleus and suppressed the DNA-binding activity of NF-κB. Furthermore, LJ significantly inhibited phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK 1/2), p38 mitogen-activated protein kinases (MAPKs), phosphatidylinositol 3-kinases (PI3K)/Akt, and Janus kinase 1 (JAK1)/signal transducer and activator of transcription (STAT)1/3. Collectively, our findings indicated that the antineuroinflammatory properties of LJ in LPS-induced BV-2 microglial cells is due to downregulation of proinflammatory cytokines and chemokines downstream of inhibition of NF-κB activation.

Abstract: Ethnopharmacological relevance: The dried flowers of Lonicera japonica Thunb and dried roots of Anemarrhena asphodeloides BUNGE have been used for the treatment of a variety of inflammatory diseases in traditional Korean medicine. Objective: The aim of the study is to evaluate the anti-inflammatory effects of WIN-34B, a new herbal medicine, in fibroblast-like synoviocytes (FLS) obtained from patients with osteoarthritis (OA). Materials and methods: WIN-34B is isolated from the n-butanol fraction of dried flowers of L. japonica and dried roots of A. asphodeloides. The anti-inflammatory effects of WIN-34B on cell viability, the production and release of inflammatory mediators, matrix metalloproteinases (MMPs), aggrecanases, tissue inhibitor of matrix proteinases (TIMP) is compared with celecoxib in IL-1β-stimulated human OA FLS. Furthermore, the effect of WIN-34B on inhibitory kappa B-α (IκB-α) phosphorylation and mitogen-activated protein kinases (MAPK) in the IL-1β-stimulated OA FLS was also evaluated. Results: WIN-34B significantly inhibited the IL-1β-induced cell viability in human OA FLS without cytotoxicity. Compared to celecoxib, WIN-34B exhibited similar or better anti-inflammatory effects through significant suppression of inflammatory mediators (IL-1β, TNF-α, PGE2 and NO), MMPs (MMP-1, MMP-3 and MMP-13) and aggrecanases (ADAMTS-4 and ADAMTS-5), and enhancement of TIMPs (TIMP-1 and TIMP-3). Moreover, WIN-34B reduced the phosphorylation of IκB-α, ERK1/2, p38 and JNK1/2 in IL-1β-stimulated OA FLS. Conclusions: WIN-34B exhibited similar or better anti-inflammatory properties in IL-1β-stimulated OA FLS compared to celecoxib. The anti-inflammatory effects of WIN-34B are due to inhibition of inflammatory mediators (IL-1β, TNF-α, PGE2 and NO) and regulation of MMPs, ADAMTSs and TIMPs via the inhibition of IκB-α and MAPK phosphorylation in IL-1β-stimulated OA FLS. [Copyright &y& Elsevier]

Lonicera japonica Thunb and Anemarrhena asphodeloides BUNGE have been used for the treatment of a variety of inflammatory diseases, cold and infective diseases in many countries, including Korea and China. Aim of the study: : This study aimed to assess the anti-nociceptive and anti-inflammatory activities of n-butanol fraction (WIN-34B) prepared from dried flowers of Lonicera japonica and dried roots of Anemarrhena asphodeloides as potential novel treatment of osteoarthritis. Materials and methods: : Anti-nociceptive activities of WIN-34B (100, 200 and 400mg/kg, p.o.) were measured using acetic acid-induced writhing response, formalin-induced paw licking, hot plate, radiant heat tail-flick, carrageenan-induced paw pressure, and Hargreaves tests, respectively. Anti-inflammatory activities of WIN-34B (100, 200 and 400mg/kg, p.o.) were assessed using acetic acid-induced vascular permeability, carrageenan-induced paw edema, and croton oil-induced ear edema. Anti-osteoarthritis effect of WIN-34B was analyzed using monosodium iodoacetate (MIA)-induced osteoarthritis animal model. Results: : WIN-34B exhibited better anti-inflammatory activity than that of celecoxib in carrageenan at the dose of 200mg/kg and croton oil-induced paw edema and ear edema at the doses of 200 and 400mg/kg. WIN-34B exhibited significant anti-inflammatory effects on vascular permeability. WIN-34B also exhibited significant anti-nociceptive activities in the late phase of formalin-induced paw licking and writhing response model in mice. In radiant heat tail-flick and carrageenan-induced paw pressure tests, WIN-34B at the dose of 400mg/kg and at the doses of 200 and 400mg/kg presented similar activities to indomethacin and celecoxib. Compared to indomethacin WIN-34B at 400mg/kg showed similar or better anti-nociceptive activities after 1 and 2h of theraphy in the hot plate test and better anti-nociceptive activity than that of celecoxib in Hargreves test. In the MIA-induced osteoarthritis animal models, WIN-34B at 400mg/kg exhibited similar or better anti-nociceptive property than that of celecoxib throughout the pain measurement periods. Conclusion: : When compared to celecoxib, WIN-34B exhibited similar or better anti-nociceptive and anti-inflammatory activities in osteoarthritic animal models, which may become a potential novel treatment for osteoarthritis. [Copyright &y& Elsevier]