Rapid characterization the chemical constituents of Bergenia purpurascens and explore potential mechanism in treating osteoarthritis by ultra high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry combined with network pharmacology.

In recent years, direct and indirect evidence has been found of the efficacy of the traditional Chinese medicine Bergenia purpurascens in treating arthritis and osteoarthritis. Several major components, such as bergenin and 11-O-galloylbergenin, have good anti-inflammatory activity. Since research on the chemical components of Bergenia purpurascens and related mechanisms for the treatment of osteoarthritis has never been performed, this study aimed to analyze the chemical components of Bergenia purpurascens through ultra high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry technology and the UNIFI screening platform to predict the underlying mechanisms in treating osteoarthritis by analyzing the network pharmacology. In total, 43 chemical constituents were identified, mainly flavonoids (18), phenolic glycosides (13), and organic acids (7). Among them, 16 components were found in Bergenia purpurascens for the first time. Through the analysis of network pharmacology, several potential candidate targets and pathways were initially predicted, including AKT1, MAPK1, and MAPK3, as well as the apoptosis, estrogen, and MAPK signaling pathways. Bergenin, 11-O-galloylbergenin, arbutin, catechin-3-O-gallate, and other components play a synergistic role in treating osteoarthritis. This study analyzed the chemical components of Bergenia purpurascens and preliminarily revealed potential mechanisms of treating osteoarthritis, providing a basis for further evaluating the drug's efficacy.

Shuangxia decoction alleviates p-chlorophenylalanine induced insomnia through the modification of serotonergic and immune system.

As a Traditional Chinese Medicine (TCM), Shuangxia Decoction (SXD) has been used to treat insomnia in oriental countries for more than thousands of years and it presents remarkable clinical effects. However, its active pharmacological fraction and the mechanism of sedative-hypnotic effects have not been explored. In this paper, we investigated active pharmacological fraction and revealed the detailed mechanisms underlying the sedative-hypnotic effects of SXD. It showed that SXD water extract compared to ethanol extract possessed better sedative effects on locomotion activity in normal mice and increased sleep duration in subhypnotic dose of sodium pentobarbital-treated mice. SXD alleviated p-chlorophenylalanine (PCPA) -induced insomnia by increasing the content of 5-HT in cortex [F (4, 55) = 12.67], decreasing the content of dopamine (DA) and norepinephrine (NE). Furthermore, SXD enhanced the expression of 5-HT1A and 5-HT2A receptors in hypothalamic and reduced serum levels of IL-1,TNF-α [F (5, 36) = 15.58]. In conclusion, these results indicated that SXD produced beneficial sedative and hypnotic bioactivities mediated by regulating the serotonergic and immune system.

Correction to: Shuangxia decoction alleviates p-chlorophenylalanine induced insomnia through the modification of serotonergic and immune system.

The original article contains mistake. The authors want to add Wenhui Pei as first co-author and Fang Fang as co-corresponding author.

Integrating UPLC-QE-Orbitrap-MS technology and network pharmacological method to reveal the mechanism of Bailemian capsule to relieve insomnia.

Bailemian capsule (BLMC) is a Chinese patent drug for treating insomnia with excellent curative effects. But there are few researches on it. In this research, a rapid separation and identification method using UPLC-QE-Orbitrap-MS was established, and 228 identified compounds were separated within 18 min. The structures of compounds were preliminarily determined by comparing the retention time and fragmentation law. Furthermore, multiple databases were used to integrate the compound targets of BLMC and the disease targets related to insomnia. After the intersection of the two sets of targets, a protein-protein interaction network and a drug-target-disease pharmacological network were established, then using the DAVID database to perform GO analysis and KEGG analysis on the common targets to find related pathways. Finally, a total of 289 common targets and 136 pathways were found to participate in the mechanism.

LC-MS-Based Qualitative Analysis and Pharmacokinetic Integration Network Pharmacology Strategy Reveals the Mechanism of Phlomis brevidentata H.W.Li Treatment of Pneumonia.

Phlomis brevidentata H.W.Li Radix (PbR) is a rare traditional Tibetan medicine, and it is widely used in the Chinese Tibetan region for the treatment of pharyngitis, pneumonia, and so forth. Nevertheless, there is very little research on its modern pharmacy, and the active ingredients and mechanisms against these diseases remain unknown. In this study, we employed the qualitative analysis and pharmacokinetic based on LC-MS technology and network pharmacology to explore the active ingredients and mechanisms of PbR for treatment of pneumonia. Ultraperformance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC-Q-TOF/MS) methodology was applied to identify the chemical composition of PbR. Meanwhile, a UPLC-MS/MS method was developed to quantify three active constituents (sesamoside, shanzhiside methyl ester, and barlerin) in rat plasma for the pharmacokinetic analysis after oral administration of PbR. Finally, in order to clarify the anti-pneumonia mechanism of this rare Tibetan medicine, a comprehensive network pharmacology strategy was applied. As a result, a total of 23 compounds were identified in PbR, including 14 iridoid glycosides, 7 phenylethanoid glycosides, and 2 other kinds of compounds. Pharmacokinetic studies have shown that the three compounds exhibit extremely similar pharmacokinetic characteristics, possibly due to their highly analogous chemical structure. We speculate that the iridoid glycosides may be the main active component in PbR. Then, the three iridoid glycoside constituents absorbed into blood were subjected to network pharmacology analysis for treatment of pneumonia. Compound-target-disease, gene ontology bioanalysis, KEGG pathway, and other network pharmacology analysis methods were applied to reveal that five main targets of the three iridoid glycosides, namely, GAPDH, ALB, MAPK1, AKT1, and EGFR, were significant in the regulation of the above bioprocesses and pathways. These results provide a basis for elucidating the bioactive compounds and the pharmacological mechanisms of P. brevidentata H.W.Li radix under clinical applications.

Integrated Screening of Effective Anti-Insomnia Fractions of Zhi-Zi-Hou-Po Decoction via Drosophila melanogaster and Network Pharmacology Analysis of the Underlying Pharmacodynamic Material and Mechanism.

Insomnia is an anabatic epidemiology, while the mechanism is extremely complicated; it remains one of the major scientific challenges in life sciences. Because of the advantage of having a similar genetic background and circadian rhythm as those of humans, the Drosophila melanogaster model organism is hugely popular in sleep-related drug screening studies. Seven-day-old virgin D. melanogaster was used to establish the sleep deprivation model by repeated light stimulation at night. Using PySolo activity monitoring system and Drosophila activity as indices, the effective fractions of Zhi-Zi-Hou-Po decoction (ZZHPD) for insomnia were screened; the content of monoamine neurotransmitters dopamine (DA), 5-hydroxyindole-3-acetic acid (5-HIAA), Homovanillic acid (HVA), and 5-hydroxytryptamine (5-HT) in the brain of D. melanogaster were determined by high-performance liquid chromatography-electro-chemical detection. The herb-compound-target-disease target network were further constructed through network pharmacology to identify the potential targets and pathways of ZZHPD in the intervention of insomnia. Finally, the molecular docking method was used for evaluating the binding characteristics of important compounds from ZZHPD with related targets. The results showed that a certain dose of ZZHPD and its petroleum ether, dichloromethane, ethyl acetate, and n-butanol fractions could improve sleep. The dichloromethane fraction from ZZHPD extracts showed the best anti-insomnia effect among all extracts. It can also reduce the content of DA and HVA in the brain of D. melanogaster and increase 5-HT and 5-HIAA levels. The network pharmacology showed that the main active ingredients in ZZHPD included magnolol, honokiol, hesperidin, and so forth. According to the screening conditions, there were 71 targets and the result of KEGG enrichment analysis revealed that 73 pathways were associated with insomnia, which were primarily involved in inflammatory response, central neurotransmitter regulation, and apoptosis to relieve insomnia. The molecular docking results clarified that naringenin and apigenin have an intimate relationship with GABAA receptor, histamine H1, orexin receptor type 2, and interleukin-6. The mechanism of relieving insomnia is the result of the interaction of multi-components, multi-targets, and multi-pathways, which provides a certain theoretical basis for the treatment of insomnia and related diseases as well as clinical research.

Bidirectional regulation of i-type lysozyme on cutaneous wound healing.

OBJECTIVE: This study aimed to assess the effect and mechanism of i-type lysozyme on cutaneous wound healing animal model and Multiple cell models both in vivo and in vitro. METHODS: Therefore, to evaluate its regenerative efficacy on wound healing process, we daily applied i-type lysozyme on murine full-thickness excisional wounds. After sacrifice on indicated days, skin tissues around surgical defects were harvested and assessed for re-epithelialization, granulation tissue formation, neovascularization and remodeling. To elucidate the underlying mechanisms, i-type lysozyme was analyzed for its tissue regenerative potency on the proliferation, invasion, migration and tube formation against keratinocytes, fibroblasts and endothelial cells. Antioxidant and antimicrobial experiments were also conducted to elucidate protective ability of i-type lysozyme to wound bed. RESULTS: It displayed excellent bi-directional regulation in wound repair, with significant acceleration of epidermal and dermal regeneration as well as the efficient attenuation of excessive collagen deposition and fibrosis in the surgical lesion. I-type lysozyme treatment augmented the proliferation and migration of HaCaT, NIH 3T3 and HUVECs, enhanced the invasion of HaCaT and HUVECs as well as accelerated tube formation of HUVECs. Additionally, it significantly recovered the proliferation of H2O2-damaged cells, whereas represented no microbicidal effect under effective concentration of wound healing. CONCLUSION: Our findings demonstrate the bi-directional regulation of i-type lysozyme in wound healing process through promoting tissue regeneration while hampering scar formation, implying that it is a promising therapeutic agent for wound repair.