A homogeneous Lonicera japonica polysaccharide alleviates atopic dermatitis by promoting Nrf2 activation and NLRP3 inflammasome degradation via p62.

ETHNOPHARMACOLOGICAL RELEVANCE: Lonicera japonica Thunb. is a traditional medicinal herb with a long history owing to its widespread use in Asia for the treatment of several inflammatory diseases including allergic dermatitis; however, its active components and mechanism of action have not been fully elucidated. AIM OF THE STUDY: In this study, a homogeneous polysaccharide with strong anti-inflammatory effects was extracted from the traditional Chinese medicine Lonicera japonica. The mechanism by which the polysaccharide WLJP-025p regulates p62 to activate Nrf2, promote NLRP3 inflammasome degradation, and improve AD was investigated. MATERIALS AND METHODS: An AD model was established using DNCB, and saline was used as a control. The WLJP-L and WLJP-H groups were administered 30 and 60 mg/kg WLJP-025p during the model challenge period, respectively. The therapeutic effect of WLJP-025p was evaluated by determining the skin thickness, performing HE and toluidine blue staining, detecting TSLP via IHC, and determining serum IgE and IL-17 levels. Th17 differentiation was detected using flow cytometry. IF and WB were performed to evaluate the expression levels of c-Fos, p-p65, NLRP3 inflammatory bodies, autophagy pathway, ubiquitination, and Nrf2 proteins. RESULTS: WLJP-025p significantly inhibited DNCB-induced skin hyperplasia and pathological abnormalities and increased TSLP levels in mice. The differentiation of Th17 in the spleen, IL-17 release, p-c-Fos, p-p65 protein expression, and NLRP3 inflammasome activation in the skin tissues were reduced. Furthermore, p62 expression, p62 Ser403 phosphorylation, and ubiquitinated proteins were increased. CONCLUSIONS: WLJP-025p improved AD in mice by upregulating p62 to activate Nrf2 and promote the ubiquitination and degradation of NLRP3.

Mechanism of Response of Watershed Water Quality to Agriculture Land-Use Changes in a Typical Fuel Ethanol Raw Material Planting Area-A Case Study on Guangxi Province, China.

Speeding up the promotion and application of biofuel ethanol has been a national strategy in China, which in turn has affected changes in the raw material planting structure. This study analyzed the response mechanism of water quality to agriculture land-use changes in a cassava fuel ethanol raw material planting area. The results revealed that an increase in cultivated land and construction land would lead to a rise in the load of TN (total nitrogen) and TP (total phosphorus), while an expansion in forest land and grassland area would reduce the load. As for crop structures, corn would have a remarkable positive impact on TN and TP, while rice and cassava performed in an opposite manner. Furthermore, scenarios under the carbon neutralization policy were carried out to forecast the nonpoint source pollutants based on the quantitative relations coefficients. It was proven that cassava planting was suitable for vigorous fuel ethanol development, but the maximum increase area of cassava should be 126 km2 to ensure economic benefits. Under the change in fuel ethanol policy, this study could provide scientific support for local agriculture land-use management in realizing the carbon neutralization vision and also set a good example for the development of the cassava fuel ethanol industry in other cassava-planting countries.

Research progress on the protective effects of aucubin in neurological diseases.

CONTEXT: Aucubin (AU), an iridoid glycoside that is one of the active constituents of Eucommia ulmoides Oliv. (EUO) (Eucommiaceae), a traditional Chinese medicine, has been extensively studied in the management of neurological diseases (NDs). However, a comprehensive review of its effects and mechanisms in this regard is currently not available. OBJECTIVE: To compile the protective effects and mechanisms of AU in NDs and provide a basis for further research. METHODS: We used 'aucubin' as the 'All Fields' or 'MeSH' in PubMed, Web of Science and China National Knowledge Infrastructure without any limitation to search all relevant articles as comprehensively as possible; we selected the articles on AU treatment of NDs for summary. RESULTS: Studies reviewed herein reported that AU improved the symptoms or prognosis of Parkinson's disease, Alzheimer's disease, intracerebral haemorrhage, diabetic encephalopathy, epilepsy, anxiety and depression, and traumatic brain injury. The pharmacological mechanisms involved in repairing neuronal loss were postulated to include increasing γ-aminobutyric acid (GABA) content in the synapse, promoting differentiation of neural precursor cells into GABAergic neurons, providing antioxidant and anti-neuroinflammation activities, as well as enhancing autophagy and anti-apoptotic actions. DISCUSSION AND CONCLUSIONS: The protective effects of AU on some NDs have been confirmed. According to the pharmacological effects, AU is also highly likely to have protective effects on other NDs, which can be realized by further in vivo and in vitro basic research, and clinical trials. In the future, AU may be used for clinical prevention or treatment of patients with neurological diseases.

The Efficacy of Needle-Warming Moxibustion Combined with Hyperbaric Oxygen Therapy for Ischemic Stroke and Its Effect on Neurological Function.

OBJECTIVE: To elucidate the therapeutic efficacy of needle-warming moxibustion (NWM) combined with hyperbaric oxygen therapy (HBOT) in the treatment of patients with ischemic stroke and its effect on neurological function. METHODS: One hundred patients with ischemic stroke admitted to the Xuzhou Medical University Affiliated Hospital of Lianyungang from January 2019 to July 2021 were enrolled. Among them, 45 patients treated with NWM were set as the control group, and the rest 55 patients treated by NWM combined with HBOT were included in the research group. The curative effect, neurological deficit score, activity of daily living (ADL), balance ability, and the levels of serum proinflammatory factors in both groups were observed and recorded. Of them, the neurological deficit of patients was evaluated by the National Institutes of Health Stroke Scale (NHISS), the ADL ability was determined by the Barthel index score, and the balance ability was assessed by the Berg balance scale. RESULTS: The total effective rate of the research group was higher than that of the control group. Better ADL and balance ability and milder neurologic impairment were determined in the research group compared with the control group. After treatment, the secretion levels of proinflammatory factors such as C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-8 (IL-8) in the serum of patients in the research group were statistically lower than those before treatment and the control group. CONCLUSIONS: NWM combined with HBOT is effective in the treatment of patients with ischemic stroke, which can not only improve patients' neurological function, ADL, and balance ability but also inhibit serum inflammatory reactions.

Distribution Characteristics and Risk Assessment of Agricultural Land Use Non-Point Source Pollution in Typical Biofuel Ethanol Planting Areas.

Speeding up the promotion and application of bio-fuel ethanol was a national strategy in China, which in turn affected changes in the raw material planting structure. This study analyzed the distribution of nitrogen and phosphorus forms in water bodies and the soil of the typical maize and cassava fuel ethanol raw material planting areas. The results revealed that the maize planting area faced more serious TN and TP pollution. The river pollution was greatly affected by TN, TP, Ex-P and Fe/Al-P in soil, while soil TN and NO3--N were the main factors influencing its counterpart. Furthermore, the risk assessment of soil nitrogen and phosphorus loss was carried out based on planting structures of crops. We investigated whether the water quality indexes or soil nitrogen and phosphorus loss risk assessment results showed that the Yujiang River stayed significantly less polluted. It was proven that the cassava planting area was more suitable for vigorously developing fuel ethanol. As for the high-risk areas, ecological agriculture promoting and fertilizer controlling measures were suggested. Under the change of the fuel-ethanol policy, this study could provide scientific support for the assessment of the impact of the Chinese national fuel ethanol policy on the water environment of the raw material planting area.

Potential Molecular Target Prediction and Docking Verification of Hua-Feng-Dan in Stroke Based on Network Pharmacology.

OBJECTIVE: Hua-Feng-Dan (HFD) is a Chinese medicine for stroke. This study is to predict and verify potential molecular targets and pathways of HFD against stroke using network pharmacology. METHODS: The TCMSP database and TCMID were used to search for the active ingredients of HFD, and GeneCards and DrugBank databases were used to search for stroke-related target genes to construct the "component-target-disease" by Cytoscape 3.7.1, which was further filtered by MCODE to build a core network. The STRING database was used to obtain interrelationships by topology and to construct a protein-protein interaction network. GO and KEGG were carried out through DAVID Bioinformatics. Autodock 4.2 was used for molecular docking. BaseSpace was used to correlate target genes with the GEO database. RESULTS: Based on OB ≥ 30% and DL ≥ 0.18, 42 active ingredients were extracted from HFD, and 107 associated targets were obtained. PPI network and Cytoscape analysis identified 22 key targets. GO analysis suggested 51 cellular biological processes, and KEGG suggested that 60 pathways were related to the antistroke mechanism of HFD, with p53, PI3K-Akt, and apoptosis signaling pathways being most important for HFD effects. Molecular docking verified interactions between the core target (CASP8, CASP9, MDM2, CYCS, RELA, and CCND1) and the active ingredients (beta-sitosterol, luteolin, baicalein, and wogonin). The identified gene targets were highly correlated with the GEO biosets, and the stroke-protection effects of Xuesaitong in the database were verified by identified targets. CONCLUSION: HFD could regulate the symptoms of stroke through signaling pathways with core targets. This work provided a bioinformatic method to clarify the antistroke mechanism of HFD, and the identified core targets could be valuable to evaluate the antistroke effects of traditional Chinese medicines.

Fractionation and antioxidant activities of the water-soluble polysaccharides from Lonicera japonica Thunb.

L. japonica has been used as food and healthy beverage due to the good nutrition. Although the chemical compounds have been extensively studied, polysaccharide compositions remain unclear. In this study, water-soluble polysaccharides of L. japonica were fractionated into one neutral fraction (LJP-N) and four acidic fractions (LJP-A-1 ~ LJP-A-4) by a combination of ion-exchange and gel permeation chromatographies. The structures and antioxidant activities of these factions were determined by HPLC, FT-IR and the radical scavenging activities, anti-hemolysis inhibitory ability, protective effect against DNA damage. Results showed that LJP-N was a starch-like glucan with some arabinogalactan; acidic fractions were all pectic polysaccharide, with the average molecular weights approximately ranging from 19.0 to 383.8 kDa. LJP-A-2 ~ LJP-A-4 were similar to each other, mainly composed of GalA (>50%) with some Gal and Ara residues, while LJP-A-1 mainly composed of Gal and Ara (>70%). LJP-A-3 was defined as HG-type pectic polysacchride, with a trace of RG-I domain by NMR experiment. The antioxidant activity of LJP fractions showed different activities, and LJP-A-3 and LJP-A-4 exhibited noticeable antioxidant activities by six kinds of evaluated methods comparable with others. The results indicated that LJP-A-3 and LJP-A-4 could be used as a potential natural source of antioxidant.

[Effect of acupoint catgut embedding, fire needle, auricular acupuncture on female post-adolescent acne and serum sex hormone].

OBJECTIVE: To compare the difference of serum sex hormone between female patients with post-adolescent acne and healthy women, and to explore the efficacy and action mechanism of acupoint catgut embedding, fire needle, auricular acupuncture on skin lesion in female patients of post-adolescent acne. METHODS: A total of 107 female patients of post-adolescent acne were divided into an integrated acupuncture group (54 cases, 4 cases were excluded) and a medication group (53 cases, 5 cases were excluded). The patients in the integrated acupuncture group were treated with comprehensive treatment of acupoint catgut embedding, fire needle, auricular acupuncture; the acupoint catgut embedding was applied at Dazhui (GV 14), Yintang (GV 29), Yangbai (GB 14) through Yuyao (EX-HN 4) and other acupoints based on syndrome differentiation; the fire needle was applied at skin lesion; the auricular acupuncture was applied at erjian (HX6，7i), e (AT1), kou (CO1), etc. The patients in the medication group were treated with oral administration of tanshinone capsules (4 capsules each time, 3 times a day) and external use of adapalene gel (one treatment per day at night). Patients in the two groups were treated for 8 weeks. The skin lesion of acne was evaluated before treatment as well as 4 weeks and 8 weeks after treatment in the two groups; the serum levels of testosterone (T) and estradiol (E2) were tested 24 hours before menstruation in the integrated acupuncture group (50 cases) and healthy control group (46 cases), and the change of serum sex hormone after treatment was observed in 21 patients with sex hormone disorder in the integrated acupuncture group. RESULTS: Before treatment, the level of E2 in the integrated acupuncture group was significantly lower than that in the healthy control group (P<0.01), but T/E2 in the integrated acupuncture group was significantly higher than that in the healthy control group (P<0.01). After treatment, the level of E2 was significantly increased (P<0.01) and T/E2 was reduced (P<0.01) in the 21 patients with sex hormone disorder in the integrated acupuncture group. The skin lesion scale of acne was significantly reduced in the two groups after 4-week and 8-week treatment (all P<0.01); the difference between the two groups was not significant after 4-week treatment (P>0.05); the skin lesion scale of acne in the integrated acupuncture group was significantly lower than that in the medication group after 8-week treatment (P<0.01). The efficacy between the two groups was not significant after 4-week the treatment (P>0.05); after 8-week treatment, the cured and effective rate was 66.0% (33/50) in the integrated acupuncture group, which was superior to 45.8% (22/48) in the medication group (P<0.05). CONCLUSION: Compared with healthy women, the level of serum sex hormone of E2 is reduced in the female patients of post-adolescent acne, resulting in relative increased level of T; the acupoint catgut embedding, fire needle, auricular acupuncture have better efficacy than medication for post-adolescent acne, which have regulation effects on sex hormone disorder.

Two new glycosides from the fruits of Forsythia suspense.

Two new glycosides suspensaside C (1) and 2,3,5,6-tetrahydro-jacaranone-4-O-ß-D-glucopyranoside (2), together with four known compounds suspensaside A (3), rengynic acid-1'-O-ß-D-glucopyranoside (4), forsythoside A (5), and rengynic acid (6), were isolated from the fruits of Forsythia suspense (Thunb.) Vahl. The structures of 1 and 2 were elucidated on the basis of chemical and spectral analysis, including 1D, 2D NMR analyses and HR-ESI-MS. All isolates were tested for their cytotoxicities against five human cancer cell lines (A549, Colo-205, Hep-3B, HL60, and KB). Compound 3 exhibited cytotoxicity against HL-60, Hep-3B, and A549 cancer cell lines.