Indonesian Journal of Pharmacology and Therapy

Phyto therapeutic potential of Andrographis paniculata and Catharanthus roseus extract against colorectal cancer HCT-116 cell line

Tue, 14 Oct 2025 00:00:00 +0700

Colorectal cancer (CRC) is the third most common cancer globally and the second leading cause of cancer-related mortality, with over 1.9 million new cases and 935,000 deaths reported in 2020. Despite therapeutic advances, recurrence, drug resistance, and systemic toxicity remain major challenges. Natural products with
antioxidant and cytotoxic activity are increasingly investigated as complementary therapies. Andrographis paniculata (Sambiloto), rich in andrographolide, exerts anticancer effects by inducing apoptosis, inhibiting migration and invasion, and modulating PI3K/Akt and NF-κB signalling pathway. Catharanthus roseus (Tapak
Dara) produces vinca alkaloids, including vincristine and vinblastine, which inhibit microtubule polymerization and are widely used in chemotherapy. Combining these extracts may enhance efficacy and reduce toxicity through synergistic interactions. This in vitro study assessed the cytotoxic and synergistic effects
of A. paniculata extract (APE) and C. roseus extract (CRE) on HCT-116 colorectal cancer cells. Extracts were prepared by ethanol maceration, and cytotoxicity was evaluated using the MTT assay at concentrations ranging from 5 to 100 μg/mL. IC₅₀ values were calculated using linear regression, and the combination index
(CI) was determined at 1, 1/2 and 1/4 IC₅₀ to evaluate synergism. APE and CRE exhibited comparable cytotoxicity, with IC₅₀ values of 90 μg/mL and 89.5 μg/mL, respectively. The combination treatment revealed synergistic effects (CI <1) at multiple ratios, particularly at 1/4 IC₅₀ (CI = 0.58), demonstrating enhanced
cytotoxicity at reduced concentrations. Both APE and CRE demonstrated significant cytotoxic effects against HCT-116 cells. Their combination produced synergistic interactions, suggesting potential as complementary phytotherapeutic agents for CRC with the benefits of dose reduction and minimized toxicity. Further in vivo and mechanistic studies are warranted.

Multi Organ Dysfunction (MODS): A life-threatening aspect of traumatic brain injury

Akshita Garg, Nidhi Khatri, Bhanu Pratap Singh, Shweta Yadav, Arti Gupta — Tue, 14 Oct 2025 00:00:00 +0700

Traumatic Brain Injury (TBI) is not only a leading cause of neurological impairment but also a critical trigger for systemic complications. Among these, Multiple Organ Dysfunction Syndrome (MODS) represents one of the most severe and life-threatening outcomes. Following a primary brain insult, secondary pathophysiological cascades—such as neuroinflammation, oxidative stress, autonomic dysregulation, and the release of damage-associated molecular patterns (DAMPs)—initiate a systemic inflammatory response that affects peripheral organs including the lungs, liver, kidneys, and heart. This brain–body cross-talk results in multi-organ dysfunction, which significantly worsens prognosis and increases mortality. Understanding the mechanisms linking TBI to MODS is essential for early diagnosis, targeted therapeutic interventions, and improved patient survival. This review highlights the underlying pathophysiology, affected organ systems, and emerging management strategies to mitigate the systemic consequences of traumatic brain injury.

Association of IMPDH1 and IMPDH2 gene polymorphisms with efficacy and toxicity of mycophenolic acid treatment in renal transplant patients: a narrative review

Dimo Pratama, Zullies Ikawati, Adam Hermawan — Tue, 14 Oct 2025 00:00:00 +0700

Immunosuppressive regimen treatment in renal transplant recipients is necessary to prevent acute rejection from the body’s immune system. Mycophenolic acid (MPA), commonly prescribed for renal transplant recipients, exists in two formulations: mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS). Both drugs act by inhibiting inosine-5’-monophosphate dehydrogenase (IMPDH), an enzyme that is responsible for the guanosine nucleotide synthesis pathway of T and B lymphocytes. IMPDH exists in two isoforms, IMPDH1 and IMPDH2, encoded by IMPDH1 and IMPDH2 gene, respectively. Polymorphisms in these genes may alter the enzyme activity, potentially influencing MPA pharmacodynamics and leading to variations in therapeutic responses among renal transplant patients taking MPA. A systematic literature search was performed using Scopus, PubMed, and Web of Science with the Boolean search strategy: “IMPDH AND Polymorphism* AND Mycophenol* AND ((Renal OR Kidney) Transplant* OR Graft*)”. The articles yielded from this literature search were screened, resulting in 15 articles that were included in this review. Some studies reported the association between the IMPDH1 or IMPDH2 polymorphism and acute rejection, while others found no significant correlation. Regarding toxicity, leukopenia was linked to IMPDH1 SNPs (rs2278293, rs2278294), although the results were inconsistent. Most of the studies found no significant association between IMPDH2 SNPs and leukopenia incidence.

Ethical consideration of gene therapy in Indonesian HIV patients and its management: A narrative review

Sun, 12 Oct 2025 00:00:00 +0700

Human Immunodeficiency Virus (HIV) infection remains a major global health issue, including in Indonesia. Gene therapy (GT) has emerged as a promising therapeutic approach for various diseases, including HIV. However, its application also raises significant ethical challenges, particularly within the Indonesian context. This article aims to explore the ethical considerations, potential, and challenges of implementing GT for patients with HIV in Indonesia. A comprehensive narrative review was conducted by examining current
scientific literature and ethical frameworks related to GT and HIV management, with a focus on clinical feasibility, safety, and social implications within the Indonesian context. Gene therapy technologies such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and Clustered
Regularly Interspaced Short Palindromic Repeats (CRISPR) have shown promising potential in suppressing HIV infection. However, concerns remain regarding onand off-target effects that may cause genomic instability and oncogenesis. Ethical challenges include the high cost of therapy, limited public understanding of GT,
and the absence of specific regulations governing its application in HIV treatment. Indonesia’s diverse sociocultural landscape further complicates equitable access and acceptance of this advanced technology. The implementation of GT for HIV in Indonesia requires careful ethical consideration, transparent communication,
and robust policy development. Establishing national guidelines and conducting further research are essential to ensure that the adoption of GT is safe, equitable, and ethically responsible within the Indonesian healthcare system.

Cost-effectiveness of immune checkpoint inhibitors and chemotherapy in triple-negative breast cancer: a scoping review

Sun, 12 Oct 2025 00:00:00 +0700

Triple-negative breast cancer (TNBC) is an aggressive malignancy associated with poor clinical outcomes and substantial economic burden. Standard chemotherapy treatment offers limited survival benefits, whereas immune checkpoint inhibitors (ICIs) have broadened therapeutic options. This review evaluates the cost-effectiveness of ICIs compared to conventional chemotherapy in TNBC and aims to identify which ICI provides the most favorable economic value. Using the PICO framework, which focuses on TNBC patients receiving chemotherapy as intervention and ICIs as comparators. The primary outcomes include incremental cost-effectiveness ratio (ICER), quality-adjusted life years (QALYs), and/or life years gained (LYG). The
articles were selected based on the PRISMA strategy. A comprehensive selection of articles published from January 2020 to December 2024 was analyzed from PubMed, Google Scholar, Cochrane, and Scopus. TNBC commonly shows high tumor T-cell infiltration and Programmed Death Ligand-1 (PD-L1) expression, making ICIs such as atezolizumab and pembrolizumab viable treatment options. Atezolizumab improved
progression-free survival (PFS) but was not found to be cost-effective in Singapore or the U.S. Pembrolizumab, however, significantly improved event-free survival (EFS) and demonstrated cost-effective across multiple countries, including Egypt, the United States of America (USA), and Switzerland. Sacituzumab govitecan, despite
survival benefits in metastatic TNBC, showed high ICERs and poor cost-effectiveness. Pembrolizumab combined with chemotherapy appears to be more cost-effective than atezolizumab for PD-L1-positive TNBC patients. Meanwhile, sacituzumab govitecan has not been demonstrated to be cost-effective.