Adjunctive Natural Multitarget Therapy in Glioblastoma is Associated with Improved Functional Status and MRI Stabilization

Abstract Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor, characterized by therapy resistance, chronic neuroinflammation, metabolic dysregulation, and defective apoptotic signaling. Novel low-toxicity, multitarget strategies capable of modulating the tumor microenvironment are urgently needed. This study aimed to evaluate associations between adjunctive integrative natural multitarget therapy (Majmui Rakhmoniy, Shifoi Markhabakhon, and Askaltsiy) and functional status (Karnofsky Performance Scale [KPS]), magnetic resonance imaging [MRI]-based tumor dynamics, systemic inflammatory markers (C-reactive protein [CRP], interleukin-6 [IL-6]), and apoptosis in primary GBM cultures. This prospective, observational study evaluated the clinical, radiological, biochemical, and cellular effects of an integrative natural multitarget therapy consisting of Majmui Rakhmoniy, Shifoi Markhabakhon, and Askaltsiy in 102 patients with histologically confirmed GBM receiving standard supportive care. Treatment duration ranged from 6 to 24 months. Apoptotic activity was assessed in primary GBM cell cultures using Annexin V-fluorescein isothiocyanate (FITC)-conjugated antibody/propidium iodide (PI) flow cytometry. Clinical outcomes included neurological symptom burden, KPS, MRI-based tumor dynamics, and systemic inflammatory markers (CRP, IL-6). In vitro, Majmui Rakhmoniy and Askaltsiy induced robust, dose-dependent apoptosis (up to 56.8%) via programmed apoptotic pathways with negligible necrosis (<1%). Clinically, an observed improvement in functional and neurological status was noted, with a mean KPS increase of approximately 30 points. MRI stabilization or partial regression was observed in 74% of patients, with age-dependent responsiveness favoring younger cohorts. Systemic inflammation was significantly reduced, with CRP and IL-6 decreasing by approximately 45%, strongly correlating with radiological stabilization (r = 0.71, p < 0.01). Long-term administration was well-tolerated, with no clinically relevant toxicity. Adjunctive administration of these natural multicomponent formulations was associated with improvements in neurological, inflammatory, and radiological parameters in this observational cohort. These preliminary observational findings provide a biologically plausible rationale for future controlled clinical investigations but should not be interpreted as evidence of therapeutic efficacy.