Persicae Semen Promotes Bone Union in Rat Fractures by Stimulating Osteoblastogenesis through BMP-2 and Wnt Signaling.

Fractures cause extreme pain to patients and impair movement, thereby significantly reducing their quality of life. However, in fracture patients, movement of the fracture site is restricted through application of a cast, and they are reliant on conservative treatment through calcium intake. Persicae semen (PS) is the dried mature seeds of Prunus persica (L.) Batsch, and in this study the effects of PS on osteoblast differentiation and bone union promotion were investigated. The osteoblast-differentiation-promoting effect of PS was investigated through alizarin red S and Von Kossa staining, and the regulatory role of PS on BMP-2 (Bmp2) and Wnt (Wnt10b) signaling, representing a key mechanism, was demonstrated at the protein and mRNA levels. In addition, the bone-union-promoting effect of PS was investigated in rats with fractured femurs. The results of the cell experiments showed that PS promotes mineralization and upregulates RUNX2 through BMP-2 and Wnt signaling. PS induced the expression of various osteoblast genes, including Alpl, Bglap, and Ibsp. The results of animal experiments show that the PS group had improved bone union and upregulated expression of osteogenic genes. Overall, the results of this study suggest that PS can promote fracture recovery by upregulating osteoblast differentiation and bone formation, and thus can be considered a new therapeutic alternative for fracture patients.

Exploring the Anti-Osteoporotic Potential of Daucosterol: Impact on Osteoclast and Osteoblast Activities.

Osteoporosis is a debilitating condition characterized by reduced bone mass and density, leading to compromised structural integrity of the bones. While conventional treatments, such as bisphosphonates and selective estrogen receptor modulators (SERMs), have been employed to mitigate bone loss, their effectiveness is often compromised by a spectrum of adverse side effects, ranging from gastrointestinal discomfort and musculoskeletal pain to more severe concerns like atypical fractures and hormonal imbalances. Daucosterol (DC), a natural compound derived from various plant sources, has recently garnered considerable attention in the field of pharmacology. In this study, we investigated the anti-osteoporosis potential of DC by characterizing its role in osteoclasts, osteoblasts, and lipopolysaccharide (LPS)-induced osteoporosis. The inhibitory effect of DC on osteoclast differentiation was determined by tartrate-resistant acid phosphatase (TRAP) staining, F-actin ring formation by fluorescent staining, and bone resorption by pit formation assay. In addition, the calcification nodule deposition effect of osteoblasts was determined by Alizarin red S staining. The effective mechanisms of both cells were verified by Western blot and reverse transcription polymerase chain reaction (RT-PCR). To confirm the effect of DC in vivo, DC was administered to a model of osteoporosis by intraperitoneal administration of LPS. The anti-osteoporosis effect was then characterized by micro-CT and serum analysis. The results showed that DC effectively inhibited osteoclast differentiation at an early stage, promoted osteoblast activity, and inhibited LPS-induced bone density loss. The results of this study suggest that DC can treat osteoporosis through osteoclast and osteoblast regulation, and therefore may be considered as a new therapeutic alternative for osteoporosis patients in the future.

Dendrobium nobile Lindley Administration Attenuates Atopic Dermatitis-like Lesions by Modulating Immune Cells.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that can significantly affect daily life by causing sleep disturbance due to extreme itching. In addition, if the symptoms of AD are severe, it can cause mental disorders such as ADHD and suicidal ideation. Corticosteroid preparations used for general treatment have good effects, but their use is limited due to side effects. Therefore, it is essential to minimize the side effects and study effective treatment methods. Dendrobium nobile Lindley (DNL) has been widely used for various diseases, but to the best of our knowledge, its effect on AD has not yet been proven. In this study, the inhibitory effect of DNL on AD was confirmed in a DNCB-induced Balb/c mouse. In addition, the inhibitory efficacy of inflammatory cytokines in TNF-α/IFN-γ-induced HaCaT cells and PMACI-induced HMC-1 cells was confirmed. The results demonstrated that DNL decreased IgE, IL-6, IL-4, scratching behavior, SCORAD index, infiltration of mast cells and eosinophils and decreased the thickness of the skin. Additionally, DNL inhibited the expression of cytokines and inhibited the MAPK and NF-κB signaling pathways. This suggests that DNL inhibits cytokine expression, protein signaling pathway, and immune cells, thereby improving AD symptoms in mice.

Water extract of Cnidii Rhizoma suppresses RANKL-induced osteoclastogenesis in RAW 264.7 cell by inhibiting NFATc1/c-Fos signaling and prevents ovariectomized bone loss in SD-rat.

BACKGROUND: Cnidii Rhizoma is the dried root stem of Cnidium officinale Makino. Cnidii Rhizoma (CR) has been used to treat menstrual irregularity, menstrual pain, and menopause in Korea. However, the effects and mechanisms of CR on RANKL-induced osteoclastogenesis pathway remain to be elucidated. In this study, we investigated the effects of CR on the inhibition of bone resorption of osteoclast and its mechanism RANK signaling pathway. METHODS: The anti-osteoclastogenesis of water extract of CR was measured using RAW 264.7 cell. Tartrate-resistant acid phosphatase (TRAP) assay, pit assay, reverse transcription polymerase chain reaction (RT-PCR) and western blot were performed. Moreover, the effects of CR were determined with an in vivo model using ovariectomized (OVX) rats. RESULTS: CR extract suppressed osteoclastogenesis, its activity and bone resorption activity through decreasing gene of osteoclast-related such as nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), c-Fos, etc. Moreover, CR extract prevented the bone loss in OVX rats. CONCLUSION: These results show that CR has a positive effect on menopausal osteoporosis by suppressing osteoclastogenesis.

Anti-inflammatory effect of Vaccinium oldhamii stems through inhibition of NF-κB and MAPK/ATF2 signaling activation in LPS-stimulated RAW264.7 cells.

BACKGROUND: Vaccinium oldhamii (V. oldhamii) has been reported to exert a variety of the pharmacological properties such as anti-oxidant activity, anti-cancer activity, and inhibitory activity of α-amylase and acetylcholinesterase. However, the anti-inflammatory activity of V. oldhamii has not been studied. In this study, we aimed to investigate anti-inflammatory activity of the stem extracts from V. oldhamii, and to elucidate the potential mechanisms in LPS-stimulated RAW264.7 cells. METHODS: Cell viability was evaluated by MTT assay. The determination of NO and PGE2 production was performed using Griess reagent and Prostaglandin E2 ELISA Kit, respectively. The change of mRNA or protein level was evaluated by RT-PCR and Western blot. RESULTS: Among VOS, VOL and VOF, the inhibitory effect of NO and PGE2 production induced by LPS was highest in VOS treatment. Thus, VOS was selected for the further study. VOS dose-dependently blocked LPS-induced NO and PGE2 production by inhibiting iNOS and COX-2 expression, respectively. VOS inhibited the expression of pro-inflammatory cytokines such as IL-1ß, IL-6 and TNF-α. In addition, VOS suppressed TRAP activity and attenuated the expression of the osteoclast-specific genes such as NFATc1, c-FOS, TRAP, MMP-9, cathepsin K, CA2, OSCAR and ATPv06d2. VOS inhibited LPS-induced NF-κB signaling activation through blocking IκB-α degradation and p65 nuclear accumulation. VOS inhibited MAPK signaling activation by attenuating the phosphorylation of ERK1/2, p38 and JNK. Furthermore, VOS inhibited ATF2 phosphorylation and blocked ATF2 nuclear accumulation. CONCLUSIONS: These results indicate that VOS may exert anti-inflammatory activity by inhibiting NF-κB and MAPK/ATF2 signaling. From these findings, VOS has potential to be a candidate for the development of chemopreventive or therapeutic agents for the inflammatory diseases.

dl-Malic acid as a component of α-hydroxy acids: effect on 2,4-dinitrochlorobenzene-induced inflammation in atopic dermatitis-like skin lesions in vitro and in vivo.

Background: dl-Malic acid (dl-M) is used widely in cosmetic formulations as a pH-adjuster or as a preservative. dl-M is used as an exfoliator in the form of α-hydroxy acids. However, the role of dl-M in skin diseases (including atopic dermatitis (AD)) has not been studied deeply. We wished to reveal the effect of dl-M on AD induced by 2,4-dinitrochlorobenzene (DNCB) in Balb/c mice.Methods: The thickness and immune-cell infiltration into the dermis and epidermis were evaluated. Moreover, serum levels of cytokines, as well as expression of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) in tissue were measured in AD mice. We also studied the effect of dl-M on inflammatory mediators in a human keratinocyte (HaCaT) cell line. Results: The dl-M (high) group improved skin condition compared with the DNCB-treated group. The dl-M (high) group inhibited phosphorylation of MAPK and NF-κB in skin tissue. dl-M reduced serum levels of interleukin-4 and IgE. Finally, dl-M decreased the expression of thymus and activation-regulated chemokine, monocyte chemoattractant protein-1 and intercellular cell adhesion molecule induced by interferon-gamma/tumor necrosis factor-α in HaCaT cells. Discussion: These results suggest that dl-M can improve the skin conditions of AD mice.

Antiallergic effects of peiminine through the regulation of inflammatory mediators in HMC-1 cells.

Peiminine is the main biologically active component derived from Fritillaria ussuriensis. Peiminine was investigated in various pulmonary diseases, but its antiallergic effect and the related mechanism have not been reported yet. The present study aimed to evaluate the effect of peiminine on mast cell-mediated allergic inflammation in HMC-1 cells. The pro-inflammatory cytokine production was measured using ELISA, reverse transcription-polymerase chain reaction and nuclear factor-kappaB (NF-κB), mitogen-activated protein kinases (MAPKs) pathway activation, as determined by Western blot analysis. Peiminine inhibits the production of the pro-inflammatory cytokine, such as interleukin (IL)-6, IL-8, tumor necrosis factor-alpha (TNF-α) and IL-1beta (IL-1ß). It was shown to have inhibitory effects on MAPKs phosphorylation and NF-B expression in human mast cells (HMC)-1 using Western blot. HMC-1 cells were observed for confirmation of histamine release. Passive cutaneous anaphylaxis (PCA) reactions were evaluated using an animal model and peiminine demonstrated inhibitory effects on IgE-dependent anaphylaxis. These results suggest that peiminine has regulatory potential for allergic inflammatory reactions mediated by HMC-1 cells.

Ursodeoxycholic acid alleviates atopic dermatitis-associated inflammatory responses in HaCaT and RBL-2H3 cells and DNCB/DFE-treated mice.

AIMS: Ursodeoxycholic acid (UDCA) is a hydrophilic dihydroxy bile acid used for cholestatic liver disease and exhibits antioxidant, antitumor, and anti-inflammatory effects. However, its potential effects on atopic dermatitis (AD) have not been elucidated. This study aimed to evaluate the efficacy of UDCA in inhibiting the inflammatory response and alleviating lesions in AD-like mice. MAIN METHODS: To investigate the efficacy of UDCA in AD-like inflammatory responses, tumor necrosis factor-alpha (TNF-α)- and interferon-gamma (IFN-γ)-stimulated HaCaT cells and anti-dinitrophenyl immunoglobulin E (DNP-IgE)- and human serum albumin (HSA)-stimulated RBL-2H3 cells were used to investigate the levels of inflammatory factors and their mechanisms. AD-like lesions were induced by applying DNCB/DFE to mice. The effect of UDCA administration in AD-like mice was analyzed by assessing organ weight, serum IgE and inflammatory cytokine levels, and histopathological changes using immunohistochemical and immunofluorescent staining. KEY FINDINGS: In HaCaT cells, UDCA significantly diminished TARC, MDC, MCP-1, and IL-6 expression by inhibiting the phosphorylation of nuclear NF-κB and cytoplasmic IκB, and also increased the levels of skin barrier protein. In RBL-2H3 cells, UDCA reduced ß-hexosaminidase and IL-4 levels. In AD-like mice, UDCA suppressed organ hypertrophy, ear edema, SCORAD index, DFE-specific IgE levels, inflammatory cytokine levels, skin hypertrophy, mast cell invasion, skin barrier loss, and thymic stromal lymphopoietin-positive areas. SIGNIFICANCE: UDCA suppressed the expression of pro-inflammatory cytokines by keratinocytes and mast cells. It also alleviated atopy by suppressing symptoms without organ toxicity in AD-like mice. UDCA may be an effective and safe treatment for AD.

Suppression of bone resorption by Mori Radicis Cortex through NFATc1 and c-Fos signaling-mediated inhibition of osteoclast differentiation.

BACKGROUND: Mori Radicis Cortex (MRC) is the root bark of the mulberry family as Morus alba L. In Korea, it is known as "Sangbaegpi". Although MRC has demonstrated anti-inflammatory and antioxidant effects, its specific mechanisms of action and impact on osteoporosis remain poorly understood. METHODS: To investigate the antiosteoporosis effect of MRC, we examined the level of osteoclast differentiation inhibition in receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced-RAW 264.7 cells and animal models of ovariectomy (OVX) with MRC. Serum analysis in OVX animals was investigated by enzyme-linked immunosorbent assay (ELISA), and bone density analysis was confirmed by micro-computed tomography (micro-CT). The expression analysis of nuclear factor of activated T cells 1 (NFATc1) was confirmed by immunohistochemistry (IHC) in femur tissue. In addition, osteoclast differentiation inhibition was measured using tartrate-resistant acid phosphatase (TRAP). mRNA analysis was performed using reverse transcription-polymerase chain reaction (RT-PCR), and the protein expression analysis was investigated by western blot. RESULTS: Micro-CT analysis showed that MRC effectively inhibited bone loss in the OVX-induced rat model. MRC also inhibited the expression of alkaline phosphatase (ALP) and TRAP in serum. Histological analysis showed that MRC treatment increased bone density and IHC analysis showed that MRC significantly inhibited the expression of NFATc1. In RANKL-induced-RAW 264.7 cells, MRC significantly reduced TRAP activity and actin ring formation. In addition, MRC significantly inhibited the expression of NFATc1 and c-Fos, and suppressed the mRNA expression. CONCLUSION: Based on micro-CT, serum and histological analysis, MRC effectively inhibited bone loss in an OVX-induced rat model. In addition, MRC treatment suppressed the expression of osteoclast differentiation, fusion, and bone resorption markers through inhibition of NFATc1/c-Fos expression in RANKL-induced RAW 264.7 cells, ultimately resulting in a decrease in osteoclast activity. These results demonstrate that MRC is effective in preventing bone loss through inhibiting osteoclast differentiation and activity.

Schizonepeta tenuifolia inhibits the development of atopic dermatitis in mice.

Historically, Schizonepeta tenuifolia (ST) has been used for the treatment of skin disorders, such as allergic dermatitis, eczema, and inflammatory diseases. In this study, we examined whether ST inhibited 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD) in BALB/c mice. In histopathological analyses of the epidermis and dermis, skin thickness was significantly increased in DNCB-induced mice as compared with normal group. Treatment with ST inhibited this inflammatory change and markedly suppressed the secretion of immunoglobulin E, tumor necrosis factor α, and interleukin 6 levels in the serum of DNCB-induced mice. In addition, ST treatment significantly restored the upregulation of proinflammatory factors, such as nuclear factor (NF)-κB and mitogen-activated protein kinase expression. Taken together, due to its ability to suppress inflammatory factors and upregulate proinflammatory factors, ST may be useful as a therapeutic treatment for AD. ST extract application decreased both epidermis and dermis thickness in DNCB-induced mice. In serum, ST reduced immunoglobulin E, tumor necrosis factor, and interleukin 6 level. In addition, ST suppressed NF-κB activation as well as the mitogen-activated protein kinase activities.

[6]-Shogaol inhibits the production of proinflammatory cytokines via regulation of NF-κB and phosphorylation of JNK in HMC-1 cells.

[6]-Shogaol is a major bioactive component of Zingiber officinale. Although [6]-shogaol has a number of pharmacological activities including antipyretic, analgesic, antitussive and anti-inflammatory effects, the specific mechanisms of its anti-allergic effects have not been studied. In this study, we present the effects of [6]-shogaol on mast cell-mediated allergic reactions in vivo and in vitro. Sprague-Dawley rats received intradermal injections of anti-DNP IgE was injected into dorsal skin sites. After 48 h, [6]-shogaol was administered orally 1 h prior to challenge with DNP-HSA in saline containing 4% Evans blue through the dorsal vein of the penis. In addition, rat peritoneal mast cells (RPMCs) were cultured and purified to investigate histamine release. In vitro, we evaluated the regulatory effects of [6]-shogaol on the level of inflammatory mediators in phorbol 12-myristate 13-acetate plus calcium ionomycin A23187-stimulated human mast cells (HMC-1). [6]-Shogaol reduced the passive cutaneous anaphylaxis reaction compared to the control group, and histamine release decreased significantly following the treatment of RPMCs with [6]-shogaol. In HMC-1 cells, [6]-shogaol inhibited the production of TNF-α, IL-6 and IL-8, as well as the activation of nuclear factor-κB (NF-κB) and phosphorylation of JNK in compound 48/80-induced HMC-1 cells. [6]-shogaol inhibited mast cell-mediated allergic reactions by inhibiting the release of histamine and the production of proinflammatory cytokines with the involvement of regulation of NF-κB and phosphorylation of JNK.

A study on specific factors related to inflammation and autophagy in BEAS-2B cells induced by urban particulate matter (PM, 1648a) and histological evaluation of PM-induced bronchial asthma model in mice.

As particulate matter (PM) poses an increasing risk, research on its correlation with diseases is active. However, researchers often use their own PM, making it difficult to determine its components. To address this, we investigated the effects of PM with known constituents on BEAS-2B cells, examining cytokine levels, reactive oxygen species ROS production, DNA damage, and MAPK phosphorylation. Additionally, we evaluated the effects of PM on normal and OVA-induced asthmatic mice by measuring organ weight, cytokine levels, and inflammatory cells in bronchoalveolar lavage fluid, and examining histological changes. PM markedly increased levels of IL-6, GM-CSF, TNF-α, ROS, nitric oxide, and DNA damage, while surprisingly reducing IL-8 and MCP-1. Moreover, PM increased MAPK phosphorylation and inhibited mTOR and AKT phosphorylation. In vivo, lung and spleen weights, IgE, OVA-specific IgE, IL-4, IL-13, total cells, macrophages, lymphocytes, mucus generation, and LC3II were higher in the asthma group. PM treatment in asthmatic mice increased lung weight and macrophage infiltration, but decreased IL-4 and IL-13 in BALF. Meanwhile, PM treatment in the Nor group increased total cells, macrophages, lymphocytes, and mucus generation. Our study suggests that PM may induce and exacerbate lung disease by causing immune imbalance via the MAPK and autophagy pathways, resulting in decreased lung function due to increased smooth muscle thickness and mucus generation.

Gleditsiae fructus regulates osteoclastogenesis by inhibiting the c­Fos/NFATc1 pathway and alleviating bone loss in an ovariectomy model.

Medical and economic developments have allowed the human lifespan to extend and, as a result, the elderly population has increased worldwide. Osteoporosis is a common geriatric disease that has no symptoms and even a small impact can cause fractures in patients, leading to a serious deterioration in the quality of life. Osteoporosis treatment typically involves bisphosphonates and selective estrogen receptor modulators. However, these treatments are known to cause severe side effects, such as mandibular osteonecrosis and breast cancer, if used for an extended period of time. Therefore, it is essential to develop therapeutic agents from natural products that have fewer side effects. Gleditsiae fructus (GF) is a dried or immature fruit of Gleditsia sinensis Lam. and is composed of various triterpenoid saponins. The anti­inflammatory effect of GF has been confirmed in various diseases, and since the anti­inflammatory effect plays a major role in inhibiting osteoclast differentiation, GF was expected to be effective in osteoclast differentiation and menopausal osteoporosis; however, to the best of our knowledge, it has not yet been studied. Therefore, the present study was designed to examine the effect of GF on osteoclastogenesis and to investigate the mechanism underlying inhibition of osteoclast differentiation. The effects of GF on osteoclastogenesis were determined in vitro by tartrate­resistant acid phosphatase (TRAP) staining, pit formation assays, filamentous actin (F­actin) ring formation assays, western blotting and reverse transcription­quantitative PCR analyses. Furthermore, the administration of GF to an animal model exhibiting menopausal osteoporosis allowed for the analysis of alterations in the bone microstructure of the femur using micro­CT. Additionally, assessments of femoral tissue and serum were conducted. The present study revealed that the administration of GF resulted in a reduction in osteoclast levels, F­actin rings, TRAP activity and pit area. Furthermore, GF showed a dose­dependent suppression of nuclear factor of activated T­cells cytoplasmic, c­Fos and other osteoclastogenesis­related markers.

Dolichos Lablab Linné Inhibits Bone Density Loss and Promotes Bone Union in Senile Osteoporosis through Osteogenesis.

As populations continue to age, osteoporosis has emerged as an increasingly critical concern. Most advancements in osteoporosis treatment are predominantly directed toward addressing abnormal osteoclast activity associated with menopause, with limited progress in developing therapies that enhance osteoblast activity, particularly in the context of aging and fractures, and serious side effects associated with existing treatments have highlighted the necessity for natural-product-based treatments targeting senile osteoporosis and fractures. Dolichos lablab Linné (DL) is a natural product traditionally used for gastrointestinal disorders, and its potential role in addressing bone diseases has not been extensively studied. In this research, we investigated the anti-osteoporosis and bone-union-stimulating effects of DL using the SAMP6 model, a naturally aged mouse model. Additionally, we employed MC3T3-E1 cells to validate DL's osteoblast-promoting effect and to assess the involvement of core mechanisms such as the BMP-2/Smad and Wnt/ß-catenin pathways. The experimental results revealed that DL promoted the formation of osteoblasts and calcified nodules by upregulating both the BMP-2/Smad and Wnt/ß-catenin mechanisms. Based on its observed effects, DL demonstrated the potential to enhance bone mineral density in aged osteoporotic mice and promote bone union in fractured mice. These findings indicate the promising therapeutic potential of DL for the treatment of osteoporosis and bone-related conditions, thus warranting further investigation and potential clinical applications.

Ethyl pyruvate attenuates formalin-induced inflammatory nociception by inhibiting neuronal ERK phosphorylation.

BACKGROUND: Ethyl pyruvate (EP) possesses anti-inflammatory activity. However, the potential anti-nociceptive value of EP for the treatment of the inflammatory nociception is largely unknown. We investigated whether EP could have any anti-nociceptive effect on inflammatory pain, after systemic administration of EP (10, 50, and 100 mg/kg, i.p.), 1 hour before formalin (5%, 50 µl) injection into the plantar surface of the hind paws of rats. RESULTS: EP significantly decreased formalin-induced nociceptive behavior during phase II, the magnitude of paw edema, and the activation of c-Fos in L4-L5 spinal dorsal horn. EP also attenuated the phosphorylation of extracellular signal-regulated kinase (ERK) in the neurons of L4-L5 spinal dorsal horn after formalin injection. Interestingly, the i.t. administration of PD98059, an ERK upstream kinase (MEK) inhibitor, completely blocked the formalin-induced inflammatory nociceptive responses. CONCLUSIONS: These results demonstrate that EP may effectively inhibit formalin-induced inflammatory nociception via the inhibition of neuronal ERK phosphorylation in the spinal dorsal horn, indicating its therapeutic potential in suppressing acute inflammatory pain.

Minocycline markedly reduces acute visceral nociception via inhibiting neuronal ERK phosphorylation.

BACKGROUND: Minocycline prevents the development of neuropathic and inflammatory pain by inhibiting microglial activation and postsynaptic currents. But, how minocycline obviates acute visceral pain is unclear. The present study investigated whether minocycline had an any antinociceptive effect on acetic acid-induced acute abdominal pain after intraperitoneal (i.p.) administration of saline or minocycline 1 hour before acetic acid injection (1.0%, 250 µl, i.p.). RESULTS: Minocycline (4, 10, or 40 mg/kg) significantly decreased acetic acid-induced nociception (0-60 minutes post-injection) and the enhancement in the number of c-Fos positive cells in the T5-L2 spinal cord induced by acetic acid injection. Also, the expression of spinal phosphorylated extracellular signal-regulated kinase (p-ERK) induced by acetic acid was reduced by minocycline pre-administration. Interestingly, intrathecal introduction of PD98059, an ERK upstream kinase inhibitor, markedly blocked the acetic acid-stimulated pain responses. CONCLUSIONS: These results demonstrate that minocycline effectively inhibits acetic acid-induced acute abdominal nociception via the inhibition of neuronal p-ERK expression in the spinal cord, and that minocycline may have therapeutic potential in suppressing acute abdominal pain.

Effects of Angelica acutiloba on mast cell-mediated allergic reactions in vitro and in vivo.

The root of Angelica acutiloba is a widely used herbal medicine which has been used as a typical therapeutic for allergic diseases in traditional medicine. This study was aimed to investigate the effects of A. acutiloba on allergic reactions in in vitro and in vivo models and its mechanism of action. A. acutiloba was extracted by maceration with 80% ethanol (AAE) and standardized by high-performance liquid chromatography. We investigated the effect of AAE on phorbol-12-myristate-13-acetate plus calcium ionophore A23187 (PMACI)-induced cytokine release; phosphorylation of JNK, ERK, and p38 in human mast cell-1 (HMC-1); and compound 48/80-induced release of histamine in rat peritoneal mast cells (RPMCs). We also investigated the effects on Evans blue (EB) extravasation induced by anti-DNP IgE in rats. Treatment with 1, 10 and 100 µg/ml AAE concentration-dependently inhibited the release of cytokines (tumor necrosis factor-α, interleukin (IL) -6, and IL-8) and phosphorylation of ERK and JNK induced by PMACI in HMC-1 cells, but it did not inhibit the phosphorylation of p38. It also inhibited compound 48/80-induced histamine release in RPMCs. Oral administration of 271 mg/kg AAE inhibited EB extravasation in a passive cutaneous anaphylaxis rat model. In conclusion, AAE inhibited mast cell-derived allergic reactions by inhibiting the release of histamine, the production of pro-inflammatory cytokines, and the phosphorylation of ERK and JNK.

Effect of Taraxaci Herba on Bone Loss in an OVX-Induced Model through the Regulation of Osteoclast Differentiation.

Bone is a dynamic tissue that maintains homeostasis with a balance of osteoclasts for bone resorption and osteoblasts for bone formation. Women are deficient in estrogen after menopause, which promotes bone resorption due to excessive activity of osteoclasts, leading to osteoporosis. TH (also known as dandelion) is native to warm regions and has traditionally been used to treat gynecological diseases and inflammation. Menopause is a major cause of osteoporosis as it causes abnormal activity of osteoclasts, and various studies have shown that anti-inflammatory drugs have the potential to treat osteoporosis. We analyzed the effect of TH on osteoclast differentiation and the relevant mechanisms using RANKL. After administration of TH in a menopause-like rat model in which ovariectomy of the was rats carried out, changes in bone microstructure were analyzed via micro-CT, and the antiosteoporosis effect of TH was verified by a histological analysis. In addition, the pharmacological effects of TH in an animal model of osteoporosis were compared and analyzed with osteoporosis medications (17ß-estradiol (E2) and alendronate (ALN)). TH significantly inhibited the initial osteoclast differentiation via the NFATc1/c-Fos mechanism. In addition, bone density in the femur of osteoporotic rats was increased, and the expression of osteoclast-related factors in the serum and tissues was controlled. The results of this study provide objective evidence of the inhibitory effect of TH on osteoclastogenesis and OVX-induced bone loss.

Fritillaria ussuriensis extract inhibits the production of inflammatory cytokine and MAPKs in mast cells.

Fritillaria ussuriensis (FU, derived from the bulbs of various species of the genus Fritillaria, including Fritillaria thunbergii Miq.) is used in herbal medicine to treat conditions such as eczema, skin burns, and frostbite. In this study, we investigated the mechanism of the anti-allergy effect of FU. FU extract (80 mg/kg), orally administered to Sprague-Dawley (SD) rats, significantly inhibited the passive cutaneous anaphylaxis (PCA) reaction. It inhibited the compound 48/80-induced release of histamine from rat peritoneal mast cells in a concentration-dependent manner. Significant inhibitory effects of the FU extract on IL-6, IL-8, and TNF-α (1, 10, and 100 µg/mL) were observed in HMC-1 cells. Treatment with FU attenuated PMA plus A23187-induced phosphorylation of all three MAPKs, especially at concentrations of 10 and 100 µg/mL. Further, it (80 mg/kg) led to significant inhibition of mast-cell accumulation in ear tissue at the chronic phase. These results indicate that it inhibits allergic reactions.

Effect of Cone of Pinus densiflora on DNCB-Induced Allergic Contact Dermatitis-Like Skin Lesion in Balb/c Mice.

Cone of Pinus densiflora (CP), or Korean red pinecone, is a cluster of Pinus densiflora fruit. CP has also been verified in several studies to have anti-oxidation, anti-fungal, anti-bacterial, and anti-melanogenic effects. However, anti-inflammatory effects have not yet been confirmed in the inflammatory responses of pinecones to allergic contact dermatitis. The purpose of this study is to prove the anti-inflammatory effect of CP on allergic contact dermatitis (ACD) in vitro and in vivo. CP inhibited the expression of TSLP, TARC, MCP-1, TNF-α, and IL-6 in TNF-α/IFN-γ-stimulated HaCaT cells and MCP-1, GM-CSF, TNF-α, IL-6, and IL-8 in PMACI (phorbol-12-myristate-13-acetate plus A23187)-stimulated HMC-1 cells. CP inhibited the phosphorylation of mitogen-activated protein kinase (MAPKs), as well as the translocation of NF-κB on TNF-α/IFN-γ stimulated in HaCaT cells. In vivo, CP decreased major symptoms of ACD, levels of IL-6 in skin lesion, thickening of the epidermis and dermis, infiltration of eosinophils and mast cells, and the infiltration of CD4+ T cells and CD8+ T cells. This result suggests that CP represents a potential alternative medicine to ACD for diseases such as chronic skin inflammation.