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<p>Kukoamine A (KuA) and kukoamine B (KuB) are spermine alkaloids characterized by polyamine backbones conjugated with phenolic moieties, primarily isolated from <i>Lycium chinense</i> root bark (<i>Lycii Cortex</i>). This review comprehensively analyses their pharmacological properties, mechanistic pathways, safety profiles, and clinical potential. KuA and KuB exhibit potent antioxidant activity by scavenging reactive oxygen species, enhancing superoxide dismutase and catalase activity, and chelating Fe<sup>2+</sup>. Their anti-inflammatory effects involve neutralizing pathogen-associated molecular patterns (e.g., LPS, CpG-DNA), suppressing TLR4/9-MyD88-NF-κB signaling, and reducing pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β). Both compounds demonstrate antimicrobial efficacy against sepsis triggers (e.g., <i>E. coli</i>) by inhibiting bacterial toxin-induced inflammation. Additionally, KuA and KuB significantly improve antidiabetic outcomes by activating the AKT/GSK-3β pathway, thereby enhancing insulin sensitivity, inhibiting DPP-4 and amyloid aggregation, and ameliorating metabolic disorders. Neuroprotective roles include mitigating oxidative stress, inhibiting neuronal apoptosis (via modulation of Bax/Bcl-2 and caspase-3), and attenuating the pathology of Parkinson’s and Alzheimer’s diseases by regulating α-synuclein and iron homeostasis. Additional benefits encompass anti-osteoporotic effects through osteoblast differentiation promotion and bone mineral density preservation. Moreover, pharmacokinetic studies indicate rapid plasma distribution and urinary excretion of KuB, with Phase I/II trials confirming tolerability in healthy and septic subjects (0.06–0.24 mg/kg doses). Safety assessments reveal mild adverse events (e.g., transient headaches). Despite promising preclinical data, clinical validation remains limited. Future research should prioritize mechanistic depth, large-scale trials, and therapeutic applications for neurodegenerative, metabolic, and inflammatory diseases.</p>

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Pharmacological properties, safety, pharmacokinetic and clinical trials of kukoamine A and B

  • 期刊论文

  • 发表日期：

    2026年2月17日

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  • Ibrahim Mssillou,
  • Youness El Abdali,
  • Olja Šovljanski,
  • Meryem Bakour,
  • Hassan Laaroussi,
  • Youssra Aghoutane,
  • Edward. J. Calabrese,
  • Asaad Khalid,
  • Samah H. O. Zarroug,
  • Boutaina Louafi,
  • Dalila Bousta

摘要

Kukoamine A (KuA) and kukoamine B (KuB) are spermine alkaloids characterized by polyamine backbones conjugated with phenolic moieties, primarily isolated from Lycium chinense root bark (Lycii Cortex). This review comprehensively analyses their pharmacological properties, mechanistic pathways, safety profiles, and clinical potential. KuA and KuB exhibit potent antioxidant activity by scavenging reactive oxygen species, enhancing superoxide dismutase and catalase activity, and chelating Fe2+. Their anti-inflammatory effects involve neutralizing pathogen-associated molecular patterns (e.g., LPS, CpG-DNA), suppressing TLR4/9-MyD88-NF-κB signaling, and reducing pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β). Both compounds demonstrate antimicrobial efficacy against sepsis triggers (e.g., E. coli) by inhibiting bacterial toxin-induced inflammation. Additionally, KuA and KuB significantly improve antidiabetic outcomes by activating the AKT/GSK-3β pathway, thereby enhancing insulin sensitivity, inhibiting DPP-4 and amyloid aggregation, and ameliorating metabolic disorders. Neuroprotective roles include mitigating oxidative stress, inhibiting neuronal apoptosis (via modulation of Bax/Bcl-2 and caspase-3), and attenuating the pathology of Parkinson’s and Alzheimer’s diseases by regulating α-synuclein and iron homeostasis. Additional benefits encompass anti-osteoporotic effects through osteoblast differentiation promotion and bone mineral density preservation. Moreover, pharmacokinetic studies indicate rapid plasma distribution and urinary excretion of KuB, with Phase I/II trials confirming tolerability in healthy and septic subjects (0.06–0.24 mg/kg doses). Safety assessments reveal mild adverse events (e.g., transient headaches). Despite promising preclinical data, clinical validation remains limited. Future research should prioritize mechanistic depth, large-scale trials, and therapeutic applications for neurodegenerative, metabolic, and inflammatory diseases.