Future Journal of Pharmaceutical Sciences最新文献

Background

Aluminum is recognized for its toxicity in humans and animals. This study investigates the protective effects of Spondias mombin leaf extracts against oxidative stress, inflammation, and apoptosis in male Wistar rats. Rats were divided into nine groups, receiving 100 mg/kg AlCl₃ for 3 weeks, followed by a 2-week treatment with Spondias mombin leaf extract (SME) or its fraction (SMF) at 100 and 200 mg/kg. Brain tissues were analyzed using biochemical, molecular, and histopathological techniques.

Results

Phytochemical analysis confirmed the presence of tannins, phenols, terpenoids, flavonoids and steroids, while HPLC analysis identified kaempferol and other polyphenols, in the Spondias mombin extracts. Aluminum exposure led to increased oxidative and inflammatory damage in brain tissue as revealed by decreased glutathione concentrations and antioxidant enzyme activities, along with elevated levels of tumor necrosis factor-alpha, nitric oxide, myeloperoxidase, xanthine oxidase, and lactate dehydrogenase. Caspase-3, and BCL2 associated X (Bax) levels were also increased in AlCl₃-exposed rats. Both SME and SMF mitigated AlCl₃-induced redox imbalance, proinflammatory events, and neuronal cell death by enhancing levels of reduced glutathione and antioxidant enzyme activities, reducing the levels of inflammatory biomarkers, and preserving hippocampal formation and neuronal cell organization.

Conclusions

These findings highlight the therapeutic potential of Spondias mombin leaf extracts against aluminum-induced neurotoxic effects through their antioxidant, anti-inflammatory, and antiapoptotic properties.

Graphical abstract

Background

This is an experimental comparative study of the ameliorative effects of imatinib and ibudilast in multiple sclerosis induced in rats by cuprizone. Forty healthy adult male rats were used and divided into five groups: normal control, solvent control, multiple sclerosis model, imatinib- and ibudilast-treated groups. To detect behavioural changes, hang wire test was done for motor assessment, Morris water maze test was done to assess long-term memory, and Y-maze test was done to assess short-term memory. The tests were done on the last day of the experiment. At the end of the study, rats were sacrificed, and brains were extracted. From the brain samples, the right hemispheres were used for measurement of biochemical parameters from brain homogenates. While the left hemispheres were used for pathological and immunohistochemical examination.

Results

Treated groups showed improvement whereas ibudilast showed improvement in the behavioural tests, MAPK, IL-17, TNF-α and histopathological examination. While imatinib showed improvement in NFκB, MBP, SOD and nitric oxide.

Conclusion

Both imatinib and ibudilast had neuroprotective role in multiple sclerosis; however, ibudilast showed better results in improving neurological manifestations, biochemical and pathological parameters. This sets ibudilast as a promising drug to help slow down the pathogenesis of multiple sclerosis.

Background

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive age, characterized by a range of metabolic and reproductive complications, including insulin resistance, hyperandrogenism, and menstrual irregularities. The complexity of PCOS necessitates innovative therapeutic strategies that extend beyond conventional pharmacological treatments.

Main body

Ursolic acid (UA), a natural pentacyclic triterpenoid found in various plants, has gained significant attention for its diverse pharmacological properties including anti-inflammatory, antioxidant, anticancer, antidiabetic, antimicrobial, antihyperlipidemic, anti-obesity, neuroprotective, hepatoprotective, and cardioprotective activities. Additionally, the integration of predictive tools, such as artificial intelligence and bioinformatics databases like STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) and KEGG (Kyoto Encyclopedia of Genes and Genomes), allows for the identification of key protein targets and pathways influenced by UA, including TP53 (Tumor Protein P53), AR (Androgen Receptor), ESR1 (Estrogen Receptor 1), BCL2 (B-cell Lymphoma 2), STAT3 (Signal Transducer and Activator of Transcription 3), and IL6 (Interleukin 6). These pathways are crucial for inflammatory regulation and have been linked to the symptoms of PCOS. Further in silico studies were conducted to validate these findings, highlighting the need for additional preclinical and clinical research.

Conclusion

Comprehensive guidelines for the effective use of UA in managing PCOS are warranted to ensure optimal treatment strategies.

Background

As the use of herbal therapies alongside conventional medications continues to rise, understanding the complexities of these interactions becomes essential for ensuring patient safety and optimizing therapeutic outcomes.

Main body

Herbal remedies, sometimes referred to as phytotherapy or herbalism, use plants and plant extracts for medicinal purposes. Various plant parts, such as leaves, roots, flowers, and seeds, are used in herbal medicines to cure illnesses and enhance health. They can be applied topically or taken as tinctures, extracts, teas, or capsules. Although using herbal treatments can have therapeutic benefits, it is important to be aware of any possible interactions. When two or more herbal products are taken together, there may be interactions between them that change their effects, intensify their side effects, or reduce their efficacy. Before using herbal medicines, it is crucial to speak with your doctor because they may have side effects and interfere with prescription drugs. The possible effects that herbs may have on prescription drugs when taken combined are referred to as herb–drug interactions.

Conclusion

These interactions may result in unexpected health outcomes, an increase in adverse effects, or modifications in the effectiveness of the medication. Herbs can also affect absorption and metabolism of food. Different countries have different laws governing herbal products. They may be subject to more strict regulations in some countries, while in others they are regarded as dietary supplement.

Background

Different parts of Allanblackia floribunda, Calotropis procera, Hymenocardia acida, Irvingia gabonensis, Newbouldia laevis, and Xylopia acutiflora have been used traditionally across different parts of Cameroon to overcome infectious diseases, especially pneumonia. Hence, this study investigated the antibacterial potential of six Cameroonian medicinal plants against selected ESKAPE pathogens (Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa) as well as Streptococcus pneumoniae.

Methodology

The inhibitory activities of different extracts from six Cameroonian plants against the pathogens were evaluated by determining their MICs. Subsequently, the top four bioactive plant extracts were assessed for antibiofilm activity, time-kill kinetics, cytotoxicity (Raw and Vero cell lines), as well as antioxidant activities. Finally, the effect of the most potent extract, viz. ethanolic extract of Xylopia acutiflora steam bark, on bacterial morphology was elucidated through scanning electron microscopy while its phytochemical composition was profiled using liquid chromatography–mass spectrometry (LC–MS).

Results

Twenty-two out of the 32 prepared extracts showed significant antibacterial activity, with MICs varying from 31.5 to 1000 µg/mL. The ethanolic, methanolic, and hydroethanolic extracts from Xylopia acutifolia and ethanolic extract from Colotropix procera exhibited broad-spectrum activity, inhibiting and eradicating bacterial biofilm. Furthermore, the extract from X. acutifolia was shown to be the most effective scavenger against DPPH (IC₅₀; 83.79 ± 1.92 µg/mL) and FRAP (IC₅₀; 22.89 ± 1.36 µg/mL) radicals, while C. procera extract was the most effective against ABTS (IC₅₀; 67.95 ± 1.83 µg/mL). The extracts were demonstrated to possess low cytotoxicity on both Raw and Vero cell lines. In addition, SEM revealed that X. acutifolia elicited cell membrane rupture and consequently cytoplasm leakage in E. coli and P. aeruginosa. Twenty-four different compounds were detected in the X. acutifolia extract via LC–MS analysis, and it was hypothesized that the recorded bioactivity in the extract might be ascribed to these compounds.

Conclusion

Results from this study have scientifically validated the ethnomedicinal uses of the six Cameroonian plants as therapeutics for infections with X. acutiflora ethanolic extract displaying the highest bioactivity. Thus, there is the need for further investigations into phytochemicals from these plants as they could serve as important sources of novel antioxidants and antimicrobial agents.

Graphical abstract

Background

Polycystic ovarian syndrome (PCOS) is an inflammatory autophagy-deficient disorder with downregulated Nrf2. Scoparone (SCPN), a natural compound from Chinese medicine, directly activates Nrf2 and clinically showed promises in treating inflammatory disorders. Studies reported SCPN’s ability to induce autophagy; yet no study tested SCPN’s ability in correcting disturbed autophagy in PCOS. The present research aim was to examine SCPN’s influence on PCOS-associated autophagic disturbances.

Methods

PCO was induced by Letrozole (1 mg/kg, p.o.) for 21 days and SCPN (12.5 mg/kg, i.p.) either alone or in parallel with an autophagy inhibitor, 3-methyl adenine, for 7 days.

Results

Hematoxylin and eosin (H&E) staining revealed reduced ovarian cysts with mature follicles recovery with SCPN. The immunolabeled ovarian tissues demonstrated that SCPN increased nuclear factor erythroid 2-related factor 2 (Nrf2) expression together with autophagic markers Beclin1, microtubule-associated protein light chain 3 (LC3), and autophagy enzyme 7 while decreasing P62. This signaling activation may be interpreted by autophagic signals upregulation; Sirtuin 1/liver kinase B1/AMP-activated protein kinase (Sirt1/LKB1/AMPK). A downregulation of inflammatory mediators, viz. tumor necrosis factor-alpha (TNF-α) and p65-nuclear factor kappa B (NF-κB) in PCOS ovaries, is associated by restoration of estradiol and FSH/LH balance. Concomitantly, SCPN abrogated testosterone and anti-Müllerian hormone levels besides insulin resistance and leptin levels.

Conclusions

The current study showed mutual link between Nrf2 and autophagic pathway. SCPN showed anti-inflammatory character with autophagic improvement in PCOS may be through Nrf2 activation.

Background

Doxorubicin (DOX) has long been a foundational drug in cancer therapeutics. Despite its proven efficacy, the persistent challenge of mitigating its associated side effects, notably hepatotoxicity and neurotoxicity, underscores the necessity for intervention. Luteolin (LUT) is a naturally derived flavonoid with a spectrum of bioactive characteristics, involving anti-apoptotic, antioxidant, anti-inflammatory, and anti-cancer attributes. This study investigates the possible protective effect of LUT against DOX-induced hepatotoxicity and neurotoxicity, focusing on its modulation of the endoplasmic reticulum (ER) stress pathways and miRNA 199a- 5p expression. Forty-eight male Sprague Dawley rats were assigned to six groups: control, LUT (200 mg/kg), DOX (3.5 mg/kg, i.p.) administered twice per week for 3 weeks, and three treatment groups that received daily oral gavage of LUT at doses of 50, 100, and 200 mg/kg for 3 weeks alongside DOX.

Results

Behavioral assessments revealed the best improvements in rats co-treated with LUT high dose (200 mg/kg), paralleled by the mitigation of neurodegeneration in the cortex and hippocampal areas of the brain. The hepatoprotective effect of LUT (200 mg/kg) demonstrated a notable decrease in liver enzymes and restoration of hepatocytic architecture, coupled with upregulation of miRNA-199a-5p and suppression of glucose-regulated protein 78 (GRP78). LUT inhibited ER stress via suppressing the inositol-requiring enzyme 1 alpha (IRE1α)/protein kinase R-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2 alpha (eIF2α)/activating transcription factor 6 (ATF6) axes, thereby inhibiting apoptosis.

Conclusions

LUT 200 mg/kg is efficacious in alleviating DOX-induced hepatic injury and neurotoxicity via dampening ER stress pathways.

Graphical abstract

Background

Rottlerin is a natural polyphenolic compound obtained from dried ripe fruits of Mallotus philippinensis and is primarily used as a PKCδ inhibitor. The effectiveness of rottlerin was checked in the endotoxin-induced glaucoma models, focusing on its impact on intraocular pressure, inflammation, and optic nerve protection. For this study, both pure and extracted rottlerin were used. Extracted rottlerin was characterised by determining its melting point, conducting gas chromatography-mass spectrometry analysis, Nuclear magnetic resonance analysis, and measuring its wavelength and retardation factor. The acute toxicity study was carried out using Organization for Economic Co-operation and development guideline 405 (acute eye irritation test).

Result

Pure and extracted rottlerin showed decreased intraocular pressure and reduced inflammation, lenticular opacity, and retinal damage. These results are attributed to an increase in antioxidant levels, maintenance of lipid peroxidation, enzyme level (Na⁺ ATPase, K⁺ ATPase), ionic balance (Na⁺, K⁺), and a decrease in the level of nitric oxide.

Conclusion

Rottlerin (pure) as well as rottlerin (extracted) has demonstrated potential in managing uveitic glaucoma. Its multifaceted mechanisms not only target inflammation and oxidative stress but also promote tissue regeneration and slow disease progression. This makes rottlerin a promising candidate for further clinical research as a potential treatment for uveitic glaucoma.

Background

Due to their high risk of medication errors (MEs) and the potentially devastating thrombotic and bleeding events, anticoagulants are a class of high-risk medications that require regular monitoring by healthcare professionals. The pharmacist is in the ideal position to provide patient care during anticoagulation therapy which is still prone to inappropriate prescribing. The pharmacist is capable of anticoagulation therapy monitoring, provision of drug information, dosing protocol preparation, drug interaction screening, and educating patients. It has been demonstrated that specialized anticoagulation management programs enhance clinical safety and quality of anticoagulant therapy. This study aimed to evaluate the effect of implementing a pharmacist-led anticoagulation stewardship program in reducing anticoagulant-related MEs. We conducted a prospective pre-and post-intervention study in a tertiary hospital on 233 patients with 4132 anticoagulant doses to assess the impact of this program implementation.

Results

This study found that MEs were significantly reduced after implementing the anticoagulation stewardship program. Specifically, the “Medication without indication” and the “Incorrect dose (low dose)” types of MEs were remarkably decreased from 14.4% pre- to 3.3% post-, and from 47.6% pre- to 28.7% post-implementation, respectively. Interestingly, the “Wrong route” disappeared in the post-implementation phase of the study. The proportion of wrong doses/total doses decreased from 0.474 ± 0.044 to 0.432 ± 0.04 (p = 0.003), while category F decreased from 8.3% to 4.7% (p = 0.001). Physician adherence to evidence-based guidelines (EBG) improved as full adherence increased from 38.8 to 60.2% (p = 0.001) and non-adherence decreased from 26.7 to 3.4% (p = 0.001). These statistically significant findings further suggest valuable clinical benefits since implementing this pharmacist-led program could improve patient outcomes by reducing ME and increasing physician adherence to EBG guidelines.

Conclusions

Although the study was limited by the hospital clinical pharmacist team's working hours, as they work 12 h/day rather than 24, and hence, the program was only observed during this time, the study concluded that the anticoagulation stewardship program encouraged the safe use of anticoagulants, lessened MEs and their severity, and improved physician adherence to EBG. Future studies should assess the effect of such programs on other clinical outcomes beyond MEs and determine their impact on healthcare costs.

Clinical Trial registration: Clinicaltrials.gov: NCT03812848. Date: January 1, 2018.

Background

Clerodendrum speciosum is a hybrid of C. thomsonae and C. splendens. Many biological and phytochemical studies have been performed on C. thomsonae and C. splendens, but few studies have been conducted on C. speciosum. Its methanol extract previously showed antioxidant activity in vivo via Caenorhabditis elegans model owing to its richness in flavonoids and phenylpropanoids.

Results

Characterization of C. speciosum leaf volatile constituents (CSV) was performed via gas chromatography linked to mass spectrometry (GC–MS). This revealed the presence of 29 metabolites that belonged mainly to oxygenated monoterpenes, sesquiterpenes and their oxygenated compounds, fatty acids and their esters. The latter constituted the predominant metabolites, whereas linoleic acid (30.64%) is the major metabolite. Liquid chromatography linked to mass spectrometry (LC–MS) was performed on the ethyl acetate fraction of C. speciosum leaves (CSE). This resulted in a tentative assignment of twenty-four peaks, whereas six peaks were not identified. These identified metabolites mainly belonged to phenylpropanoids, whereas flavonoids, iridoid glycosides, phenolic acids and their derivatives were also detected. The leaf volatile constituents showed notable antiarthritic activity as evidenced by the significant inhibition of albumin denaturation with an IC₅₀ of 32.50 μg/mL comparable that of diclofenac sodium (15.12 μg/mL). The leaf ethyl acetate fraction revealed potent antioxidant effect estimated by 725.43 ± 5.95 mg TE/g, 333.82 ± 19.9 mg TE/g, 2.1 ± 0.08 mmol TE/g and 3.69 ± 0.3 mg EDTA/g. in cupric-reducing antioxidant capacity (CUPRAC), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), phosphomolybdenum (PHD) and metal-chelating activity (MCA) assays, respectively. It showed a reasonable α-glucosidase and α-amylase inhibition estimated by 1.88 ± 0.05 and 0.14 ± 0.01 mmol ACAE/g, respectively. ADME/TOPAKT assessment, processed on the prevalent identified components detected in CSV, displayed acceptable pharmacodynamic, toxicity and pharmacokinetic behaviors for most tested compounds except for n-nonadecane and n-heptacosane and n-octacosane.

Conclusion

Thus, C. speciosum leaves could serve as a promising treasure for the treatment of many diseases such as arthritis and diabetes mellitus owing to its abundance with flavonoids and terpenoidal compounds.