Pharmaceutical Biology最新文献

Context: Zhibai Dihuang pill (ZD), a traditional Chinese medicine nourishes Yin and reduces internal heat, is believed to have therapeutic effects on urinary tract infections (UTIs).

Objective: To explore the effects and mechanism of modified ZD (MZD) on UTI induced by extended-spectrum β-lactamase (ESBLs) Escherichia coli.

Materials and methods: Thirty Sprague-Dawley rats were randomly divided into control, model (0.5 mL 1.5 × 10⁸ CFU/mL ESBLs E. coli), MZD (20 g/kg MZD), LVFX (0.025 g/kg LVFX), and MZD + LVFX groups (20 g/kg MZD + 0.025 g/kg LVFX), n = 6. After 14 days of treatment, serum biochemical indicators, renal function indicators, bladder and renal histopathology, and urine bacterial counts in rats were determined. Additionally, the effects of MZD on ESBLs E. coli biofilm formation and related gene expression were analyzed.

Results: MZD significantly decreased the count of white blood cells (from 13.12 to 9.13), the proportion of neutrophils (from 43.53 to 23.18), C-reactive protein (from 13.21 to 9.71), serum creatinine (from 35.78 to 30.15), and urea nitrogen (from 12.56 to 10.15), relieved the inflammation and fibrosis of bladder and kidney tissues, and reduced the number of bacteria in urine (from 2174 to 559). In addition, MZD inhibited the formation of ESBLs E. coli biofilms (2.04-fold) and decreased the gene expressions of luxS, pfS and ompA (1.41-1.62-fold).

Discussion and conclusion: MZD treated ESBLs E. coli-induced UTI inhibited biofilm formation, providing a theoretical basis for the clinical application of MZD. Further study on the clinical effect of MZD may provide a novel therapy option for UTI.

Context: Ginkgo biloba Linn (Ginkgoaceae) [leaves extract (GBE)] is authorized for the treatment of sudden hearing loss (SHL); however, its clinical feasibility in SHL has not been thoroughly investigated.

Objective: To evaluate the efficacy and safety of adjuvant GBE in the treatment of SHL.

Materials and methods: We used PubMed, EMBASE, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang, Chinese Scientific Journal Database, China Biomedical Database for literature research, starting from inception to 30 June 2022. The key terms: Ginkgo biloba extract, Sudden Sensorineural Deafness. This meta-analysis contained randomized controlled trials that compared the safety and efficacy of the combination of GBE and general treatments (GT) with GT alone for SHL. The extracted data were analyzed using Revman5.4 software with risk ratio (RR), 95% confidence intervals (CI) and mean difference (MD).

Results: Our meta-analysis included 27 articles with a total of 2623 patients. The results revealed that the effects of GBE adjuvant therapy was superior than GT (total effective rate: RR = 1.22, 95% CI: 1.18-1.26, p < 0.00001), the pure tone hearing threshold (MD = 12.29, 95% CI: 11.74-12.85, p < 0.00001) and hemorheology indexes (whole blood high shear viscosity: MD = 1.46, 95% CI: 0.47-2.44, p = 0.004) after treatment were significantly improved compared to non-treatment, while there was no significant difference as for hematocrit (red blood cells) (MD = 4.15, 95% CI: -7.15-15.45, p = 0.47).

Conclusion: The efficacy of GBE + GT for the treatment of SHL may be more promising than GT alone.

Context: Dolichos trilobus Linn (Leguminosae) is often used in Yi ethnic medicine to treat pain, fracture, and rheumatism.

Objective: To explore the therapeutic potential of doliroside B (DB) from D. trilobus and its disodium salt (DBDS) and the underlying mechanism in pain.

Materials and methods: In the writhing test, Kunming mice were orally treated with DB and DBDS at doses of 0.31, 0.62, 1.25, 2.5, and 5 mg/kg. Vehicle, morphine, indomethacin, and acetylsalicylic acid were used as negative and positive control on the nociception-induced models, respectively. In the hot plate test, mice were orally treated with DB and DBDS at doses of 2.5, 5, 10, and 20 mg/kg. In the formalin test, mice were orally treated with DB and DBDS at doses of 2.5, 5, 10, and 20 mg/kg. In the meanwhile, lipopolysaccharide-induced inflammatory model in RAW264.7 macrophages was adopted to study the mechanism of pain alleviation for DBDS.

Results: DBDS (5 mg/kg) inhibited the writhing number by 80.2%, which exhibited the highest antinociceptive activity in pain models. DBDS could selectively inhibite the activity of COX-1. Meanwhile, it also reduced the production of NO, iNOS, and IL-6 by 55.8%, 69.0%, and 49.9% inhibition, respectively. It was found that DBDS also positively modulated the function of GABA_A1 receptor.

Discussion and conclusions: DBDS displayed antinociceptive activity by acting on both the peripheral and central nervous systems, which may act on multitargets. Further work is warranted for developing DBDS into a potential drug for the treatment of pain.

Context: Bergamot, mainly produced in the Ionian coastal areas of Southern Italy (Calabria), has been used since 1700 for its balsamic and medicinal properties. Phytochemical profiling has confirmed that bergamot juices are rich in flavonoids, including flavone and flavanone glycosides which are responsible for its beneficial effects.Objective: Recently, it was shown that the combination of natural compounds with conventional treatments improves the efficacy of anticancer therapies. Natural compounds with anticancer properties attack cancerous cells without being toxic to healthy cells. Bergamot can induce cytotoxic and apoptotic effects and prevent cell proliferation in various cancer cells.Methods: In this review, the antiproliferative, pro-apoptotic, anti-inflammatory, and antioxidant effects of bergamot are described. Information was compiled from databases such as PubMed, Web of Science, and Google Scholar using the key words 'bergamot' accompanied by 'inflammation' and, 'cancer' for data published from 2015-2021.Results: In vitro and in vivo studies provided evidence that different forms of bergamot (extract, juice, essential oil, and polyphenolic fraction) can affect several mechanisms that lead to anti-proliferative and pro-apoptotic effects that decrease cell growth, as well as anti-inflammatory and antioxidant effects.Conclusions: Considering the effects of bergamot and its new formulations, we affirm the importance of its rational use in humans and illustrate how bergamot can be utilized in clinical applications. Numerous studies evaluated the effect of new bergamot formulations that can affect the absorption and, therefore, the final effects by altering the therapeutic profile of bergamot and enhancing the scientific knowledge of bergamot.

Context: The toxicity of atractyloside/carboxyatractyloside is generally well recognized and commonly ascribed to the inhibition of mitochondrial ADP/ATP carriers, which are pivotal for oxidative phosphorylation. However, these glycosides may 'paralyze' additional target proteins.

Objective: This review presents many facts about atractyloside/carboxyatractyloside and their plant producers, such as Xanthium spp. (Asteraceae), named cockleburs.

Methods: Published studies and other information were obtained from databases, such as 'CABI - Invasive Species Compendium', 'PubMed', and 'The World Checklist of Vascular Plants', from 1957 to December 2022. The following major keywords were used: 'carboxyatractyloside', 'cockleburs', 'hepatotoxicity', 'mitochondria', 'nephrotoxicity', and 'Xanthium'.

Results: In the third decade of the twenty first century, public awareness of the severe toxicity of cockleburs is still limited. Such toxicity is often only perceived by specialists in Europe and other continents. Interestingly, cocklebur is among the most widely distributed invasive plants worldwide, and the recognition of new European stands of Xanthium spp. is provided here. The findings arising from field and laboratory research conducted by the author revealed that (i) some livestock populations may instinctively avoid eating cocklebur while grazing, (ii) carboxyatractyloside inhibits ADP/GDP metabolism, and (iii) the direct/indirect target proteins of carboxyatractyloside are ambiguous.

Conclusions: Many aspects of the Xanthium genus still require substantial investigation/revision in the future, such as the unification of the Latin nomenclature of currently distinguished species, bur morphology status, true fruit (achene) description and biogeography of cockleburs, and a detailed description of the physiological roles of atractyloside/carboxyatractyloside and the toxicity of these glycosides, mainly toward mammals. Therefore, a more careful interpretation of atractyloside/carboxyatractyloside data, including laboratory tests using Xanthium-derived extracts and purified toxins, is needed.

Context: Hydroxysafflor yellow A (HSYA) is the main bioactive ingredient of safflower (Carthamus tinctorius L., [Asteraceae]) for traumatic brain injury (TBI) treatment.

Objective: To explore the therapeutic effects and underlying mechanisms of HSYA on post-TBI neurogenesis and axon regeneration.

Materials and methods: Male Sprague-Dawley rats were randomly assigned into Sham, controlled cortex impact (CCI), and HSYA groups. Firstly, the modified Neurologic Severity Score (mNSS), foot fault test, hematoxylin-eosin staining, Nissl's staining, and immunofluorescence of Tau1 and doublecortin (DCX) were used to evaluate the effects of HSYA on TBI at the 14th day. Next, the effectors of HSYA on post-TBI neurogenesis and axon regeneration were screened out by pathology-specialized network pharmacology and untargeted metabolomics. Then, the core effectors were validated by immunofluorescence.

Results: HSYA alleviated mNSS, foot fault rate, inflammatory cell infiltration, and Nissl's body loss. Moreover, HSYA increased not only hippocampal DCX but also cortical Tau1 and DCX following TBI. Metabolomics demonstrated that HSYA significantly regulated hippocampal and cortical metabolites enriched in 'arginine metabolism' and 'phenylalanine, tyrosine and tryptophan metabolism' including l-phenylalanine, ornithine, l-(+)-citrulline and argininosuccinic acid. Network pharmacology suggested that neurotrophic factor (BDNF) and signal transducer and activator of transcription 3 (STAT3) were the core nodes in the HSYA-TBI-neurogenesis and axon regeneration network. In addition, BDNF and growth-associated protein 43 (GAP43) were significantly elevated following HSYA treatment in the cortex and hippocampus.

Discussion and conclusions: HSYA may promote TBI recovery by facilitating neurogenesis and axon regeneration through regulating cortical and hippocampal metabolism, BDNF and STAT3/GAP43 axis.

Context: Berberine is a potential drug that can effectively treat cardiovascular diseases, including premature ventricular contractions (PVCs).

Objective: This study was conducted to assess the efficacy and safety of berberine for PVCs.

Methods: The literature was searched using PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang, and Chinese Biomedical Literature Database (CBM) for randomized controlled trials (RCTs) from inception to October 1, 2022. The risk of bias was assessed using the Revised Cochrane risk-of-bias tool for randomized trials, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was adopted to assess the quality of evidence.

Results: Ten RCTs with 896 participants were included in the meta-analysis. The results showed that compared to antiarrhythmic drugs (AD), berberine (BE) combined with AD had a higher effective rate (RR = 1.26; 95% CI:1.12, 1.42; p = 0.0001) with no significant incidence of adverse reactions (RR = 0.93; 95% CI:0.33, 2.57; p = 0.88), and BE alone had no significant difference in effective rate (RR = 0.91; 95% CI:0.77, 1.07; p = 0.23), and a lower incidence of adverse reactions (RR = 0.38; 95% CI:0.15, 0.97; p = 0.04) and recurrence rate (RR = 0.40; 95% CI:0.18, 0.88; p = 0.02).

Conclusions: The results suggest that BE is an effective and safe adjunctive method for PVCs. In addition, BE is recommended for patients with PVCs who had severe adverse reactions after administrating AD as an alternative therapy.

Context: The genus Sideritis L. (Lamiaceae) is represented by 46 species in Turkey with an 79% endemism ratio, 42 of 46 belonging to the section Empodoclia.

Objective: In this review article, Sideritis species growing in Turkey have been evaluated for phytochemical constituents and biological activities.

Methods: The data for the isolates, components and extracts of the Anatolian Sideritis species and their bioactivity studies were retrieved from the main databases WoS, Scopus and PubMed from 1975 until 31 December 2022.

Results: In this review article, terpenoids, flavonoids, phenolics and other secondary metabolites isolated from Turkish Sideritis species were reported. Anatolian Sideritis species, which primarily consist of monoterpenes and sesquiterpenes, were studied in detail. Sideritis plants are represented by 46 species in Turkey, and 25 of them were investigated for their diterpenoids through isolation or LC-MS studies. Most of the diterpenoids of Turkish Sideritis species have ent-kaurene skeleton, among them linearol, siderol, 7-epicandicandiol and sideridiol were found to be the main compounds. Exceptionally, labdane, pimarane and beyerene diterpenoids were only found in a few species. For phenolics and flavonoids, only 12 species were investigated until now, and they were found to be rich in phenylethanoid glycosides and flavonoid glycosides. In terms of activity, most of the species were tested for antioxidant activity, followed by antimicrobial and anti-ulcer/anti-inflammatory activities. Their cytotoxic, enzyme inhibitory, antinociceptive and antistress activities were less frequently studied.

Conclusions: Sideritis species should be considered promising therapeutic agents in the treatment of upper respiratory tract and ulcer/inflammatory diseases.

Context: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still spreading rapidly. Relevant research based on the antiviral effects of Thesium chinense Turcz (Santalaceae) was not found.

Objective: To investigate the antiviral and anti-inflammatory effects of extracts of T. chinense.

Materials and methods: To investigate the anti-entry and replication effect of the ethanol extract of T. chinense (drug concentration 80, 160, 320, 640, 960 μg/mL) against the SARS-CoV-2. Remdesivir (20.74 μM) was used as positive control, and Vero cells were used as host cells to detect the expression level of nucleocapsid protein (NP) in the virus by real-time quantitative polymerase chain reaction (RT-PCR) and Western blotting. RAW264.7 cells were used as an anti-inflammatory experimental model under lipopolysaccharide (LPS) induction, and the expression levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay (ELISA).

Results: The ethanol extract of T. chinense significantly inhibited the replication (half maximal effective concentration, EC₅₀: 259.3 μg/mL) and entry (EC₅₀: 359.1 μg/mL) of SARS-CoV-2 into Vero cells, and significantly reduced the levels of IL-6 and TNF-α produced by LPS-stimulated RAW264.7 cells. Petroleum ether (EC₅₀: 163.6 μg/mL), ethyl acetate (EC₅₀: 22.92 μg/mL) and n-butanol (EC₅₀: 56.8 μg/mL) extracts showed weak inhibition of SARS-CoV-2 replication in Vero cells, and reduced the levels of IL-6 and TNF-α produced by LPS-stimulated RAW264.7 cells.

Conclusion: T. chinense can be a potential candidate to fight SARS-CoV-2, and is becoming a traditional Chinese medicine candidate for treating COVID-19.

Context: Er Miao San (EMS) is a formulation that contains Atractylodis Rhizoma and Phellodendri Cortex in 1:1 ratio, and is commonly used to treat rheumatoid arthritis (RA) and other inflammatory diseases.

Objective: We investigated the mechanism of action and effects of EMS on peritoneal macrophage differentiation in a rat model of adjuvant arthritis (AA).

Materials and methods: EMS (3, 1.5 and 0.75 g/kg; once daily) and methotrexate (0.5 mg/kg; once every 3 days) were administered orally from days 21 to 35 after immunisation. Paw swelling and arthritis index were measured; pathological changes in the ankle joint were observed using x-ray and haematoxylin eosin staining. The ratio of CD86/CD206 in macrophages was detected by flow cytometry. Examination of the miRNA-33/NLRP3 signalling pathway was examined by RT-qPCR and western blotting. The levels of cytokines in the serum and cell supernatants were tested by ELISA.

Results: EMS significantly reduced the AA index in rats (from 11.0 to 9.3) and pathological changes in the ankle joint (from 3.8 to 1.4). The ratio of CD86/CD206 was reduced, and polarisation to M1 improved (from 0.9 to 0.6) in macrophages of EMS-treated rats. EMS downregulated the miRNA-33/NLRP3 pathway. Furthermore, EMS treatment increased IL-10 and TGF-β levels in the serum and supernatant of macrophages of AA rats and simultaneously decreased the levels of IL-1β and TNF-α.

Discussion and conclusions: Our results suggest that EMS may reduce macrophage polarisation to the M1 inflammatory phenotype by downregulating the miRNA-33/NLRP3 pathway in AA rats. These findings may provide new insights into the treatment of RA.