Journal of Pharmaceutical Research International

Optimizing Migraine Therapy: A Comparative Review of Dosage and Tolerability of Calcitonin Gene Related Peptide Antagonists

Sarabjot Singh-Sethi-Makkar — 2025-09-13

Background: Migraines are a common neurological disorder which are characterised by recurrent headaches accompanied by ‘auras’, nausea, vomiting and photophobia.

Objective: This review summarises the role of Calcitonin gene-related peptide (CGRP) in migraine as a therapeutic and prophylactic target and evaluates the dosage strategies and tolerability of CGRP inhibitors.

Summary of Findings: CGRP is a central mediator of migraines and its inhibition is led by two major classes of therapies: the monoclonal antibodies (mAbs) and small-molecule receptor antagonists (gepants). The mAbs (erenumab, fremanezumab, galcanezumab, eptinezumab) are usually administered monthly/quarterly for prophylaxis and reduce overall monthly migraine days with favourable tolerability (mild injection site reactions seen). On the other hand, gepants (ubrogepant, rimegepant, atogepant, zavegepant) are available for use in oral and nasal formulations for both therapeutic and prophylactic use. They show moderate tolerability with acceptable gastrointestinal or neurological adverse effects. Collectively, CGRP-targeted therapies expand treatment options, offering flexibility in route, frequency, and clinical application.

Conclusion: CGRP inhibitors are a relatively new therapy which are well tolerated and effective treatments that can be individualised to each patient’s needs. Further ongoing studies are required for establishing long term safety, durability and efficacy.

Migraine in Saudi Arabia: Prevalence and Emerging Genetic Insights: A Systematic Review and Meta-Analysis

Ghadeer Ibrahim Shetefi — 2025-09-16

Introduction: Migraine is a chronic neurological disorder with recurrent headaches and aura, shaped by both environmental and genetic factors. In Saudi Arabia, rising prevalence contrasts with scarce genetic research. This study systematically reviews local evidence on migraine-related genetic markers and gaps.

Methodology: This systematic review and meta-analysis followed PRISMA and R-AMSTAR guidelines. An electronic literature search was performed from January 11, 2025 to April 15, 2025. We searched PubMed, Google Scholar, Embase, and MEDLINE (2005– until march 2025) for studies on Genetic Cause of Migraines in KSA. Two independent reviewers screened titles, abstracts, and full texts, with data extracted into Excel; disagreements resolved with discussion.

Results: In this systematic review and meta-analysis, 19 studies were included, of which 3 (15.8%) identified genetic associations with migraine. The pooled migraine prevalence across Saudi in the included studies was 3,643 out of 12,248 participants (39.8%, 95% CI: 28.4%–51.3%, I² = 99.6%, p < 0.001). Genetic subgroup analysis showed a higher migraine prevalence in studies reporting genetic associations (63.5%, 95% CI: 34.4%–92.7%) vs. non-genetic studies (35.6%, p = 0.0814). Family history subgroup analysis revealed significantly increased prevalence among those with a positive family history (62.0% vs. 31.5%, p = 0.0230). Gender-based analysis showed higher rates in female-dominant cohorts (49.4% vs. 32.3%, p = 0.1484). Genes associated with migraine included RETNLB, CYTB, ND5, and ATP1A2, all with risk-type associations, especially among migraine with aura cases. Three studies (15.8%) used whole-exome sequencing and validated findings through Sanger sequencing.

Conclusion: This review found that only 3 of 19 studies in Saudi Arabia investigated migraine genetics, underscoring a major research gap despite strong evidence of heritability. Limited findings suggest associations with nuclear and mitochondrial genes (RETNLB, CYTB, ND5, ATP1A2), particularly in migraine with aura, highlighting the urgent need for broader genomic research in this population.

Scientific Evaluation of Siddha Formulation Sirupanchamoola Kiyazham: Antimicrobial Activity, Molecular Docking and Toxicological Safety Assesments

P.Mangaiarkarasi — 2025-09-01

The Siddha system of medicine, deeply rooted in Tamil Nadu's traditional practices, emphasizes holistic health through herbal and mineral formulations. Combining antibacterial activity, molecular docking mechanisms, and toxicological safety assessments, this work offers a thorough scientific assessment of Sirupanchamoola Kiyazham (SPK), a Siddha preparation. Safety and efficacy of SPK were evaluated using advanced methods including toxicity studies in Wistar albino rats, High-Performance Thin-Layer Chromatography (HPTLC), and Thin-Layer Chromatography (TLC). The antimicrobial study verified sterility of SPK by not revealing any microbial contamination. In Docking study, the binding of solanine, quercetin, luteolin, and lupeol to Cyclooxygenase-2 (COX-II) and Prostaglandin H synthases highlights the potential of Sirupanchamoola Kiyazham as an analgesic and anti-arthritic agent, HPTLC fingerprinting identified important phytocompounds. Acute and 28-day repeated-dose oral toxicity tests as well as other toxicological evaluations found no appreciable side effects, therefore verifying the safety of SPK within clinical dosage ranges. The results confirm the therapeutic potential of SPK and support its safe integration into contemporary medicine. This research bridges the gap between traditional knowledge and scientific validation, paving the way for future clinical trials to establish its efficacy in managing pain related conditions.

Fraction-Dependent Redox Modulation by Tapinanthus globiferus Leaf Extracts Parasitizing Psidum guajava in Drosophila melanogaster

Jane-Rose I. Oche — 2025-09-03

Tapinanthus globiferus, a hemiparasitic mistletoe extensively used in African ethnomedicine, was evaluated for its redox-modulatory and cytotoxic properties using Drosophila melanogaster under non-stressed physiological conditions. Methanolic crude extract and solvent-partitioned fractions (butanol, methanol, ethyl acetate) from leaves parasitizing Psidium guajava were administered via diet supplementation (1.0 mg/10 g) for 10 days. Survival analysis revealed enhanced longevity in flies treated with the butanol (77%) and methanol (63.3%) fractions, while the crude extract significantly reduced survival (43.6%). Biochemical assays indicated pro-oxidant activity in the crude and ethyl acetate fractions, evidenced by elevated hydrogen peroxide and protein carbonyl levels (p ≤ 0.0001, p = 0.008), and antioxidant effects in the butanol and methanol fractions, marked by reduced malondialdehyde and nitric oxide levels (p < 0.05). Glutathione depletion was observed in the crude extract group (p = 0.002), while GST activity and total thiol levels remained unchanged. Gene expression analysis showed upregulation of CNC (Nrf2 homolog) by the methanol fraction (p = 0.05) and downregulation by the ethyl acetate fraction (p = 0.0006), with no significant change in SOD1 expression. The crude extract exhibited the highest cytotoxicity in MTT assays. These findings highlight the fraction-dependent redox behavior of T. globiferus, supporting the therapeutic potential of its butanol and methanol fractions while cautioning against the use of unrefined extracts due to potential pro-oxidant and cytotoxic effects.

Optimization of Green Extraction of Oil from Black Chia Seed Using Supercritical CO2 and Study of Its In-vitro Antioxidant Characteristics

Arun Kumar — 2025-09-11

Chia (Salvia hispanica L.) is an emerging oilseed crop renowned for its rich nutritional profile and diverse health-promoting properties. Black chia seed oil (BCO) is particularly valued for its high content of omega-3 fatty acids and bioactive compounds, making it a promising functional ingredient. Supercritical fluid extraction (SFE) using liquid CO₂ is preferred over conventional extraction methods, as it preserves thermolabile omega-3 fatty acids and bioactive compounds due to SFE’s controlled conditions. Therefore, optimizing the SFE process for BCO is essential to maximize yield and maintain oil quality. The extraction process was optimized using RSM with a specific focus on variables such as oil yield (%), iodine value (gI2/100g), and total phenolic content (TPC) (mg GAE/100g), having extraction independent variables: extraction pressure (X₁), extraction time (X₂), and CO₂ flow rate (X₃). A backpropagation-trained ANN has been utilized for optimal configuration prediction of each RSM response. Data analysis reported extraction pressure and CO2 flow rate as key factors. Optimal conditions were: 400 bar pressure, 3.24 h extraction time, and 18.24 g/min CO₂ flow rate. These parameters showed a 28.96 % oil yield, an iodine value of 213.78 g I2/100g, and a TPC value of 3.563 mg GAE/100g. The oil sample obtained with optimized extraction conditions was further characterized for in vitro antioxidant activities based on DPPH radical scavenging assay (64.91%), ferric reducing antioxidant power (FRAP) assay (411.78 µgAAE/g), and other assays collectively showed the potent antioxidant properties of black chia seed oil, suggesting its potential health benefits in reducing oxidative stress and enhancing overall well-being. The substantial presence of polyunsaturated fatty acids (PUFAs) and antioxidant content in black chia seed oil underscores its potential as a valuable natural resource suitable for various applications in food, cosmetics, and pharmaceuticals.