Efficacy of Mitragyna speciosa (Kratom) Extract for Diabetic Ulcer Healing: A Literature Review / Efikasi Ekstrak Mitragyna speciosa (Kratom) terhadap Penyembuhan Ulkus Diabetik: Tinjauan Literatur

Diabetic ulcers, particularly diabetic foot ulcers (DFUs), are chronic complications of diabetes mellitus characterized by persistent inflammation, oxidative stress, impaired angiogenesis, increased infection risk, and delayed tissue remodeling. Botanically derived adjuncts have gained attention because their mixed phytochemical profiles may act on several wound-healing pathways simultaneously. Mitragyna speciosa (kratom) is an alkaloid-rich Rubiaceae plant with reported anti-inflammatory, antioxidant, antimicrobial, and pro-regenerative activities. This review aimed to evaluate the current evidence on the potential role of Mitragyna speciosa extract in diabetic ulcer healing, distinguish kratom-specific evidence from broader botanical context, and identify key knowledge gaps that must be addressed before clinical translation. Methods: A PRISMA-style systematic review was conducted using an internet search engine, which returned 521 records. Records were screened against predefined population, intervention, comparator, outcome, study-design, and attribution criteria. Eight sources met the eligibility criteria and were synthesized qualitatively. Results: No clinical trial, observational study, or in vivo diabetic-wound study directly compared kratom extract with standard wound care. Kratom-specific evidence was limited to in vitro and formulation studies. The available in vitro synthesis reported suppression of tumor necrosis factor-alpha, interleukin-6, cyclooxygenase-2, 5-lipoxygenase, nitric oxide, and reactive oxygen species, as well as stimulation of cell migration and angiogenesis. A topical spray film-forming kratom formulation has been developed, but efficacy data are not yet available. Broader systematic reviews indicate that botanical adjuncts may improve DFU healing outcomes, but these reviews did not include kratom. Current evidence supports biological plausibility but does not establish comparative effectiveness. Standardized kratom formulations require in vivo validation, dose-response assessment, safety evaluation, and adequately powered randomized clinical trials before any clinical recommendation can be made.

Ulkus diabetik, khususnya ulkus kaki diabetik, merupakan komplikasi kronis diabetes melitus yang ditandai oleh inflamasi persisten, stres oksidatif, gangguan angiogenesis, peningkatan risiko infeksi, dan keterlambatan remodelling jaringan. Terapi adjuvan yang berasal dari bahan botani semakin mendapat perhatian karena profil fitokimianya yang kompleks dapat bekerja pada beberapa jalur penyembuhan luka secara bersamaan. Mitragyna speciosa (kratom) merupakan tanaman famili Rubiaceae yang kaya alkaloid dan dilaporkan memiliki aktivitas antiinflamasi, antioksidan, antimikroba, dan pro-regeneratif. Tinjauan literatur ini mengevaluasi bukti yang tersedia mengenai efektivitas ekstrak M. speciosa dibandingkan dengan perawatan luka standar dalam meningkatkan penyembuhan ulkus diabetik.Tinjauan sistematis bergaya PRISMA dilakukan melalui pencarian di internet, yang menghasilkan 521 rekam literatur. Rekam literatur disaring berdasarkan kriteria populasi, intervensi, pembanding, luaran, desain studi, dan atribusi yang telah ditetapkan sebelumnya. Delapan sumber memenuhi kriteria kelayakan dan disintesis secara kualitatif.Tidak ditemukan uji klinis, studi observasional, atau studi in vivo pada luka diabetik yang secara langsung membandingkan ekstrak kratom dengan perawatan luka standar. Bukti spesifik tentang kratom masih terbatas pada studi in vitro dan studi formulasi. Sintesis bukti in vitro yang tersedia melaporkan penekanan tumor necrosis factor-alpha, interleukin-6, cyclooxygenase-2, 5-lipoxygenase, nitric oxide, dan reactive oxygen species, disertai stimulasi migrasi sel dan angiogenesis. Formulasi kratom topikal berbentuk spray film-forming telah dikembangkan, tetapi data efikasinya belum tersedia. Tinjauan sistematis yang lebih luas menunjukkan bahwa adjuvan botani dapat meningkatkan luaran penyembuhan ulkus kaki diabetik, tetapi tinjauan tersebut tidak mencakup kratom. Bukti saat ini mendukung plausibilitas biologis, tetapi belum menetapkan efektivitas yang membandingkan. Formulasi kratom yang terstandar memerlukan validasi in vivo, penilaian hubungan dosis-respons, evaluasi keamanan, serta uji klinis acak dengan kekuatan sampel yang memadai sebelum rekomendasi klinis dapat diberikan.