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The Anti-Osteoporosis Effects of Panax japonicus via Downregulation of Inflammatory Factors: A Network Pharmacology and Ovariectomized Rat Model Study.

OBJECTIVE: Osteoporosis is a major and growing public health problem characterized by decreased bone mineral density and destroyed bone microarchitecture. Panax japonicus has been clinically used in the treatment of bone diseases, especially osteoporosis. However, there is a lack of study on the mechanism of osteoporosis treatment with Panax japonicus. MATERIALS AND METHODS: A network pharmacology approach was employed to identify the targets of osteoporosis and Panax japonicus. Cytoscape 3.7.2 and DAVID were used to visualize the pharmacological mechanism of Panax japonicus in treating osteoporosis by building up compound-target and protein-protein interaction (PPI) networks and conducting Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. An ovariectomized SD rat osteoporosis model was used to assess the potential therapeutic effect of Panax japonicus in vivo. The biomechanical properties, pathological changes, inflammatory cytokines, bone density, and bone microstructural parameters in rat bone tissue were carefully measured. The biochemical markers of bone metabolism in serum were detected by Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS AND DISCUSSION: Fifty-two active components and sixty-five target genes of Panax japonicus involved in the treatment of osteoporosis were identified. The PPI network revealed IL-6, TNF, NR3C1, IL-1β, CASP3, ESR1, PGR, and AR to be involved in the treatment of osteoporosis with Panax japonicus. Chikusetsusaponin IVa and Radix ginsenoside-Ro were the main saponins found in Panax japonicus. Panax japonicus was found to exert potent preventive effects on osteoporosis by maintaining biomechanical properties, increasing bone mineral density, and protecting the trabecular microstructure in an ovariectomized rat osteoporosis model. Panax japonicus hindered the initiation of osteoporosis induced by ovariectomy by regulating bone metabolism and downregulating the expression of IL-6 and TNF-α. CONCLUSION: Panax japonicus was found to contain 52 compounds and 65 targets in the treatment of osteoporosis. The administration of Panax japonicus could mitigate osteoporosis in rats induced by ovariectomy, and one of the mechanisms was associated with downregulating the expression of inflammatory factors.

Animals

Effects of Panax Ginseng root on conditioned avoidance response in rats.

Pole climbing and shuttle box tests were employed to study conditioned avoidance response (CAR) and discrimination behaviour in Wistar male rats given extracts from Panax Ginseng root intraperitonealy. Neutral saponins (GNS), a water soluble fraction (GF4) which does not contain saponins, and a lipid soluble fraction (GNo. 5) inhibited CAR and discrimination ability between 500 Hz sound with electric shock (SD) and 1000 Hz sound without shock (Sdelta). Small doses of GNo. 5 and ginsenoside Rg fraction (GRg) produced a slight shortening of the response latency (RL) to the conditioned stimulus in CAR. GNo. 5 produced the incorrect response to Sdelta. Significant changes in the extinction of CAR were not evident with any fraction. Data from these tests indicate that Panax Ginseng root contains at least three sedative compounds.

Animals

Comprehensive Identification of WDR Gene Family in Panax ginseng: PgWDR Gene Expression Analysis with Ginsenosides Biosynthesis Under MeJA.

Panax ginseng (Panax ginseng C.A. Mey.) produces pharmacologically valuable ginsenosides. WD40-repeat (WDR) proteins act as versatile regulators of plant specialized metabolism, yet their biological roles under methyl jasmonate (MeJA) elicitation remain largely uncharacterized in ginseng. In this study, we identified 29 PgWDR family members at the whole-genome level, and systematically analyzed their phylogeny, gene structure, cis-acting promoter elements, as well as organ- and development-dependent expression patterns. Six candidate genes potentially associated with ginsenoside biosynthesis were screened through integrating gene-metabolite correlation analysis and gene co-expression analysis. Under MeJA treatment, three of these candidates showed statistically significant expression responses, while the other three exhibited variable expression fluctuations with no statistical significance. PgWDR24 displayed a positive correlation with key ginsenoside biosynthetic enzyme genes, and a negative correlation with protopanaxadiol-type ginsenoside accumulation. Combined with its predicted nuclear localization, we hypothesize that PgWDR24 participates in the negative modulation of protopanaxadiol-type ginsenoside accumulation, although further genetic functional validation is still required. This work provides valuable candidate genes for deciphering ginsenoside regulatory networks and offers support for molecular-assisted breeding of high-quality ginseng.

Panax ginseng C. A. Mey.

Stimulatory effect of Panax ginseng principles on DNA, RNA, protein and lipid synthesis in rat bone marrow.

Effects of extract fraction 3 and 4 from the root of Panax ginseng on bone marrow cells of the rat were investigated. Oral administration of fraction 3 and addition of fraction 4 in vitro stimulated DNA, protein and lipid synthesis in bone marrow cells. The stimulatory effect was reduced by pretreatment of cycloheximide. Single i.p. injection of fraction 4 also increased DNA and RNA synthesis. Numbers of mitosis were increased by oral administration of fraction 3. Extent of the increase was almost equal in both myeloid and erythoid. Numbers of total nucleated cells in bone marrow and reticulocytes in peripheral blood were significantly increased. The hematopoiesis-stimulating action of Panax ginseng and its mechanism of the action were discussed.

Animals

Alleviation of Helicobacter pylori-Induced Pathogenicity and Gastric Inflammation by Majonoside-R2- and Ginsenoside Rg1-Rich Fractions From Panax vietnamensis Ha Et Grushv.: A Metabolomics-Guided Investigation.

Helicobacter pylori infection remains a major global health concern due to its association with gastric inflammation, ulceration, and gastric malignancies. This study evaluated the effects of Ngoc Linh ginseng (Panax vietnamensis Ha et Grushv.) root fractions on H. pylori virulence and host inflammatory responses. UHPLC-MS/MS-based metabolomic profiling coupled with feature-based molecular networking was employed to characterize the chemical profiles of different solvent fractions, identifying the dichloromethane (DCM) fraction as enriched in ginsenosides, particularly the ocotillol-type saponin majonoside R2 (MR2). In vitro assays showed that, despite minimal direct antibacterial activity, the DCM fraction at sub-inhibitory concentrations significantly reduced urease activity, acid tolerance, biofilm formation, and the expression of major virulence genes, including vacA and cagA. In H. pylori-infected AGS gastric epithelial cells, the DCM fraction and MR2 decreased VacA and CagA translocation, suppressed pro-inflammatory signaling and cytokine production, restored antioxidant defenses, and alleviated mitochondrial apoptosis. By contrast, ginsenoside Rg1 selectively modulated host inflammatory and oxidative stress responses without affecting bacterial virulence gene expression. These results demonstrate that Ngoc Linh ginseng root fractions mitigate H. pylori-induced pathogenic effects primarily through anti-virulence and host-directed mechanisms, highlighting their potential relevance for the development of gastric health-promoting functional products.

Helicobacter pylori

Ultrastructural studies on the effects of Korean Panax ginseng on the theca interna of rat ovary.

An investigation was conducted to delineate the fine structure of steroid-producing ovarian theca interna cells following administration of Korean Panax ginseng to rats for 60 days. The cytoplasmic changes were observed in the ginseng-treated theca interna cells, increased number, size and density of the mitochondria, and increased size of the smooth surfaced endoplasmic reticulum, the rough surfaced endoplasmic reticulum and the Golgi apparatus. The nucleus and nucleolus were slightly enlarged and increased numbers of dense bodies were seen whereas lipid droplets were decreased in number. The changes may result from hyperfunction of the steroid-producing cells. Morphologic changes seen may represent stimulating effects on the steroid-producing cells of the theca interna in ginseng-treated animals.

Adipose Tissue

Effects of Panax Ginseng root on acquisition of sound discrimination behaviour in rats.

Pole-climbing and shuttle-avoidance tests were employed to study the acquisition of conditioned avoidance response (CAR) and discrimination behaviour (DB) in male Wistar rats which had been given extracts from Panax Ginseng root intraperitoneally or orally. Neither a lipid soluble fraction (GNo. 5) nor a ginsenoside Rg fraction (GRg) produced significant changes in the acquisition of CAR. GRg given intraperitoneally produced a significant acceleration in the acquisition of DB between a 500 Hz signal sound followed by an electric shock (SD) and a 1000 Hz signal sound without a shock (S delta) in rats which had learned to avoid the shock following SD at a rate of over 95%. Small doses of GNo. 5 produced a significant depression in the acquisition of DB.

Animals

Chemico-pharmacological studies on saponins of Panax ginseng C. A. Meyer. II. Pharmacological part.

The pharmacological properties of seven pure saponins isolated from Panax ginseng C. A. Meyer were studied. 1. The ginseng saponins showed weak toxicities in mice. Especially, Rg1, Rf and Rb 1, which contained glucose as a sugar component, were weaker in their toxicities than the rest, which contained arabinose and/or rhamnose. It was also noted that the saponins containing protopanaxadiol as sapogenin were more toxic than those containing protopanaxatriol. 2. All the saponins diminished ACh-induced contraction of the isolated ileum of the guinea pig. On the other hand high concentrations of Rb 2 caused contraction of the ileum by itself. 3. All of the saponins induced a decrease in heart rate and showed biphasic actions on the blood pressure in rats, while they little affected respiration. They caused blood pressure fall preceded by slight rise. Among them, Rg 1 showed the most prominent action and it produced a blood pressure rise with doses of 30 to 100 mg/kg. The pressor as well as depressor action was not influenced by the pretreatment with any of atropine, diphenhydramine, phentolamine and propranolol. 4. Rg 1 and Re showed vasodilator action in dogs, the potencies of which were 1/20 and 1/50 of that of papaverine, respectively. Rc and Rb 2 showed very weak vasodilator actions but Rb 1 did not. 5. Among the 7 saponins, Rd, Re and Rb 2 showed more potent hemolytic actions than those of the rest and the potencies were proportional to their toxicities. 6. Whereas single administration of Rf, Re and Rd significantly suppressed the conditioned avoidance response, repeated administration of them caused facilitation of the response. On the other hand, Rb 2 always showed very weak suppressant action. 7. Rg 1, Rf, Re and Rd significantly suppressed the fighting of mice induced by foot shock, while Rb 1, Rb 2 and Re little affected the fighting. 8. All the saponins showed antifatigue action. They markedly increased the movement after compulsory gait and the action was consistent and independent of their action on the movement before compulsory gait. 9. The saponins showed moderate depressant actions on the EEG and the behavior in cats. They were qualitatively similar in their actions, although Rg 1, Re and Rb 2 were more potent than the rest. They also suppressed EEG arousal response induced by electrical stimulation of the mid brain in cats.

Acetylcholine

Stimulatory effect of Panax ginseng principles on DNA and protein synthesis in rat testes.

The effect of fraction 4 of the extract from the roots of Panax ginseng, Oura, on DNA and protein syntheses was investigated. Addition of fraction 4 in vitro stimulated DNA and protein syntheses in testes. The stimulating effect was reduced by pretreatment with cycloheximide. This might give some evidence about the stimulatory effect of ginseng on spermatogenesis.

Animals

Evaluation of commercial ginseng products.

The variation in panaxoside content of roots and commercial products of Panax ginseng and P. quinquefolium was evaluated by a new spectrodensitometric TLC method. The method is rapid and applicable to all commercial products, and it has a relative standard deviation of 6.4%. Panaxoside patterns of slurry-filled capsules and root extracts most closely resembled those of whole roots. Tablets did not contain detectable panaxosides while teas and granules for infusion yielded only low concentrations. The wide variation among these products indicates the need for more rigid control.

Chromatography, Thin Layer