Rosarugosides A and D from Rosa rugosa Flower Buds: Their Potential Anti-Skin-Aging Effects in TNF-α-Induced Human Dermal Fibroblasts.

This present study investigated the anti-skin-aging properties of Rosa rugosa. Initially, phenolic compounds were isolated from a hot water extract of Rosa rugosa's flower buds. Through repeated chromatography (column chromatography, MPLC, and prep HPLC), we identified nine phenolic compounds (1-9), including a previously undescribed depside, rosarugoside D (1). The chemical structure of 1 was elucidated via NMR, HR-MS, UV, and hydrolysis. Next, in order to identify bioactive compounds that are effective against TNF-α-induced NHDF cells, we measured intracellular ROS production in samples treated with each of the isolated compounds (1-9). All isolates reduced the level of ROS at a concentration of 10 µM. Particularly, two depsides-rosarugosides A and D (2 and 1)-significantly inhibited ROS expression in TNF-α-induced NHDFs compared to the other phenolic compounds. Subsequently, the production of MMP-1 and procollagen type Ι α1 by these two depsides was examined. Remarkably, rosarugoside A (2) significantly decreased MMP-1 secretion at all concentrations. In contrast, rosarugoside D (1) regulated the expression of procollagen type Ι α1. These findings collectively suggest that Rosa rugosa extracts and their isolated compounds, rosarugosides A (2) and D (1), hold significant potential for protecting against aging and skin damage. Overall, these findings suggest that Rosa rugosa extracts and their isolated compounds, rosarugosides A (2) and D (1), have the potential to prevent and protect against aging and skin damage, although more specific quantitative analysis is needed.

Inulae Flos has Anti-Depressive Effects by Suppressing Neuroinflammation and Recovering Dysfunction of HPA-axis.

Depression is a debilitating mood disorder that causes persistent feelings of sadness, emptiness, and a loss of joy. However, the clinical efficacy of representative drugs for depression, such as selective serotonin reuptake inhibitors, remains controversial. Therefore, there is an urgent need for more effective therapies to treat depression. Neuroinflammation and the hypothalamic-pituitary-adrenal (HPA) axis are pivotal factors in depression. Inulae Flos (IF), the flower of Inula japonica Thunb, is known for its antioxidant and anti-inflammatory effects. This study explored whether IF alleviates depression in both in vitro and in vivo models. For in vitro studies, we treated BV2 and PC12 cells damaged by lipopolysaccharides or corticosterone (CORT) with IF to investigate the mechanisms of depression. For in vivo studies, C57BL/6 mice were exposed to chronic restraint stress and were administered IF at doses of 0, 100, and 300 mg/kg for 2 weeks. IF inhibited pro-inflammatory mediators, such as nitric oxide, inducible nitric oxide synthase, and interleukins in BV2 cells. Moreover, IF increased the viability of CORT-damaged PC12 cells by modulating protein kinase B, a mammalian target of the rapamycin pathway. Behavioral assessments demonstrated that IF reduced depression-like behaviors in mice. We found that IF reduced the activation of microglia and astrocytes, and regulated synapse plasticity in the mice brains. Furthermore, IF lowered elevated CORT levels in the plasma and restored glucocorticoid receptor expression in the hypothalamus. Collectively, these findings suggest that IF can alleviate depression by mitigating neuroinflammation and recovering dysfunction of the HPA-axis.

Triterpenoidal Saponins from the Leaves of Aster koraiensis Offer Inhibitory Activities against SARS-CoV-2.

Triterpenoidal saponins have been reported to be able to restrain SARS-CoV-2 infection. To isolate antiviral compounds against SARS-CoV-2 from the leaves of Aster koraiensis, we conducted multiple steps of column chromatography. We isolated six triperpenoidal saponins from A. koraiensis leaves, including three unreported saponins. Their chemical structures were determined using HR-MS and NMR data analyses. Subsequently, we tested the isolates to assess their ability to impede the entry of the SARS-CoV-2 pseudovirus (pSARS-CoV-2) into ACE2+ H1299 cells and found that five of the six isolates displayed antiviral activity with an IC50 value below 10 µM. Notably, one unreported saponin, astersaponin J (1), blocks pSARS-CoV-2 in ACE2+ and ACE2/TMPRSS2+ cells with similar IC50 values (2.92 and 2.96 µM, respectively), without any significant toxic effect. Furthermore, our cell-to-cell fusion and SARS-CoV-2 Spike-ACE2 binding assays revealed that astersaponin J inhibits membrane fusion, thereby blocking both entry pathways of SARS-CoV-2 while leaving the interaction between the SARS-CoV-2 Spike and ACE2 unaffected. Overall, this study expands the list of antiviral saponins by introducing previously undescribed triterpenoidal saponins isolated from the leaves of A. koraiensis, thereby corroborating the potency of triterpenoid saponins in impeding SARS-CoV-2 infection.

Saponins Derived from the Korean Endemic Plant Heloniopsis koreana Inhibit Diffuse-type Gastric Cancer Cells.

Diffuse-type gastric cancer (GC) is a type of stomach cancer that occurs in small clusters of cells that are widely spread. It does not typically manifest with symptoms until the advanced stages and often goes undetected in routine imaging tests. In addition, there is no specific targeted therapy for diffuse-type GC and it has a high mortality risk. Hence, it is worthwhile to discover molecules against this cancer. In this study, the extract of Heloniopsis koreana, which is endemic to Korea, exhibited cytotoxicity against two diffuse-type GC cell lines, MKN1 and SNU668. This led to the isolation of 10 compounds, including a new cinnamic acid glycoside. Of the compounds, saponin Th (4) and SNF 11 (5) showed potent activities with IC50 values of 3.66 and 3.85 µM, respectively, in MKN1 cells, and 1.8 and 1.98 µM, respectively, in SNU668 cells. These compounds prevented cancer cell division, invasion, and colony formation in both cell lines. In addition, these compounds induced cancer cell death through conventional cell death pathways, showing an increase in ADP-ribose polymerase, caspase 3, and BAX and a decrease in BCL2.

The Effects of Flavonol and Flavone Glucuronides from Potentilla chinensis Leaves on TNF-α-Exposed Normal Human Dermal Fibroblasts.

Skin aging is a complex biological process influenced by a variety of factors, including UV radiation. UV radiation accelerates collagen degradation via the production of reactive oxygen species (ROS) and cytokines, including TNF-α. In a prior investigation, the inhibitory properties of flavonol and flavone glucuronides derived from Potentilla chinensis on TNF-α-induced ROS and MMP-1 production were explored. Consequently, we verified the skin-protective effects of these flavonol and flavone glucuronides, including potentilloside A, from P. chinensis, and conducted a structure-activity relationship analysis as part of our ongoing research. We investigated the protective effects of the extract and its 11 isolates on TNF-α-stimulated normal human dermal fibroblasts (NHDFs). Ten flavonol and flavone glucuronides significantly inhibited ROS generation (except for 7) and suppressed MMP-1 secretion, except for 2. In contrast, six isolates (1, 5, 6, 11, 9, 10, and 11) showed a significant reverse effect on COLIA1 secretion. Comparing the three experimental results of each isolate, potentilloside A (1) showed the most potent skin cell-protective effect among the isolates. Evaluation of the signaling pathway of potentilloside A in TNF-α-stimulated NHDF revealed that potentilloside A inhibits the phosphorylation of ERK, JNK, and c-Jun. Taken together, these results suggest that compounds isolated from P. chinensis, especially potentilloside A, can be used to inhibit skin damage, including aging.

Linderae Radix Ameliorates Cognitive Dysfunction by Inhibiting Neuroinflammation and Synaptic Damage in Alzheimer's Disease Models.

Neuroinflammation and synaptic damage are important etiologies associated with the progression of Alzheimer's disease (AD). Linderae Radix (LR) has antioxidant and anti-inflammatory properties. This study investigated whether LR attenuates microglia activation-mediated neuroinflammation and synaptic degeneration and improves AD pathological phenotypes induced by amyloid beta oligomers (AßO) or lipopolysaccharide (LPS) toxicity. For in vitro studies, we treated LR to AßO-stimulated HT22 cells or LR LPS-stimulated BV2 cells. For in vivo studies, we administered LR to mice and AßO was injected by stereotaxic to induce cognitive impairment, neuroinflammation, and synaptic loss. We found that LR increased the cell viability reduced by AßO. Moreover, LR inhibited pro-inflammatory mediators such as nitric oxide (NO), inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2), and downregulated p38 mitogen-activated protein kinase (MAPK) signaling in BV2 cells. Behavioral assessments demonstrated that LR administration significantly improved cognitive decline induced by AßO-injection. Furthermore, we found that microglia activation increased, and the expression of synaptic proteins decreased in the hippocampus of the AßO-injected group, which was alleviated in the LR-treated group. These findings suggest that LR may be a potential candidate for protection against neuroinflammation and synaptic loss, and may prevent or delay AD progression.

Magnolin Inhibits Paclitaxel-Induced Cold Allodynia and ERK1/2 Activation in Mice.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of anti-cancer drugs. The main symptoms often include sensory disturbances and neuropathic pain, and currently there is no effective treatment for this condition. This study aimed to investigate the suppressive effects of magnolin, an extracellular signal-regulated kinase (ERK) inhibitor substance derived from a 95% EtOH extract of the seeds of Magnolia denudata, on the symptoms of CIPN. A taxol-based anti-cancer drug paclitaxel (PTX) was repeatedly injected (2 mg/kg/day, total 8 mg/kg) into mice to induce CIPN. A neuropathic pain symptom was assessed using a cold allodynia test that scores behaviors of licking and shaking paw after plantar administration of acetone drop. Magnolin was administered intraperitoneally (0.1, 1, or 10 mg/kg) and behavioral changes to acetone drop were measured. The effect of magnolin administration on ERK expression in the dorsal root ganglion (DRG) was investigated using western blot analysis. The results showed that the repeated injections of PTX induced cold allodynia in mice. Magnolin administration exerted an analgesic effect on the PTX-induced cold allodynia and inhibited the ERK phosphorylation in the DRG. These results suggest that magnolin could be developed as an alternative treatment to suppress paclitaxel-induced neuropathic pain symptoms.

Effects of Artemisia annua L. on postmenopausal syndrome in ovariectomized mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia annua L. (Asteraceae) has been used as an antipyretic and anti-parasitic drug in traditional medicine for more than 2000 years. It has also been prescribed to treat symptoms caused by deficiency of Yin, which might be observed in menopausal state from the point of view of traditional medicine. AIM OF THE STUDY: We hypothesized that A. annua might be useful for treating menopausal disorders with less adverse effects than hormone replacement therapy. Thus, the aim of the present study was to investigate effects of A. annua on postmenopausal symptoms of ovariectomized (OVX) mice. MATERIALS AND METHODS: OVX mice were employed as a model for postmenopausal disorders. Mice were treated with a water extract of A. annua (EAA; 30, 100 or 300 mg/kg, p.o.) or 17ß-estradiol (E2; 0.5 mg/kg, s.c.) for 8 weeks. Open field test (OFT), novel object recognition task (NOR), Y-maze test, elevated plus maze test (EPM), splash test and tail suspension test (TST) were conducted to determine whether EAA could ameliorate postmenopausal symptoms. Phosphorylated levels of extracellular signal-regulated kinase (ERK), protein kinase B (Akt), and glycogen synthase kinase-3ß (GSK-3ß), ß-catenin and expression level of synaptophysin in the cortex and hippocampus were evaluated by Western blot analysis. RESULTS: EAA treatment significantly increased the discrimination index in NOR, decreased the time in closed arm than in open arm in EPM, increased grooming time in splash test, and decreased immobility time in TST, as did E2 treatment. In addition, decreased phosphorylation levels of ERK, Akt, GSK-3ß, and ß-catenin and expression levels of synaptophysin in the cortex and hippocampus after OVX were reversed by administration of EAA and E2. CONCLUSION: These results suggest that A. annua can ameliorate postmenopausal symptoms such as cognitive dysfunction, anxiety, anhedonia, and depression by activating ERK, Akt, and GSK-3ß/ß-catenin signaling pathway and hippocampal synaptic plasticity, and that A. annua would be a novel treatment for postmenopausal symptoms.

Inhibitory effect of ginsenglactone A from Panax ginseng on the tube formation of human umbilical vein endothelial cells and migration of human ovarian cancer cells.

Background: Here, we aimed to assess the inhibitory effect of a new compound from Panax ginseng on the migration of human ovarian cancer cells and tube formation of human umbilical vein endothelial cells (HUVECs). Methods: A new compound, ginsenglactone A (1), was isolated from ginseng roots, together with seven known compounds (2-8). Spectroscopic data were used to elucidate the chemical structure of 1. The tubular structure formation in HUVECs was assessed by Mayer's hematoxylin staining. The migration of A2780 cells was evaluated using the scratch wound healing assay. Results: HUVECs treated with 1 had the statistically significant decrease in tubular structure formation compared to the HUVECs treated with compounds 2-8. This effect was enhanced by co-treatment with inhibitors for phosphatidylinositol 3-kinase (PI3K) (LY294002) and extracellular signal-regulated kinase (ERK) (U0126). Treatment with 1 decreased the expression of phosphorylation of ERK, PI3K, vascular endothelial growth factor receptor2 (VEGFR2), Akt, and mammalian target of rapamycin (mTOR). In addition, the ability of A2780 cells to cover the scratched area were also decreased. This effect was enhanced by co-treatment with U0126. Lastly, treatment with 1 decreased the phosphorylation of ERK, matrix metalloproteinase-9 (MMP-9), and MMP-2. Conclusion: These results suggest that ginsenglactone A is a potential inhibitor of HUVEC tubular structure formation and A2780 cellular migration, which may be helpful for understanding its anticancer mechanism.

(1'S)-1'-Acetoxyeugenol Acetate Enhances Glucose-Stimulated Insulin Secretion.

Alpinia galanga have been widely used as spice or traditional medicine in East Asia, commonly known as Thai ginger. In the present study, seven major phenylpropanoids, (±)-1'-hydoxychavicol acetate (1; HCA), (1'S)-1'-acetoxychavicol acetate (2; ACA), (1'S)-1'-acetoxyeugenol acetate (3; AEA), eugenyl acetate (4), trans-p-coumaraldehyde (5), trans-p-acetoxycinnamyl alcohol (6), and trans-p-coumaryl diacetate (7), were isolated from the 95% EtOH and hot water extracts of the rhizomes of A. galanga by chromatographic method. Phenylpropanoids 1-7 were evaluated for glucose-stimulated insulin secretion (GSIS) effect and α-glucosidase inhibitory activity. Phenylpropanoids 1-4 increase GSIS effect without cytotoxicity in rat INS-1 pancreatic ß-cells. In addition, INS-1 cells were treated with AEA (3) to determine a plausible mechanism of ß-cell function and insulin secretion through determining the activation of insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3-kinase (PI3K), Akt, and pancreatic and duodenal homeobox-1 (PDX-1). Upon treatment with AEA (3), INS-1 cells showed an increase in these protein expressions. Meanwhile, AEA (3) exhibited α-glucosidase inhibitory activity. On the basis of the above findings, we suggest AEA (3) as a potential antidiabetic agent.