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<p>Multiple sclerosis (MS) is a chronic immune-mediated disorder of the central nervous system characterised by progressive neuronal demyelination. Its progression is influenced by genetic, environmental, and immunological factors, including abnormal immune responses targeting the myelin sheath. Ethidium bromide (EtBm)-induced demyelination in rat models has provided insights into MS pathology and therapeutic strategies. A total of 88 Wistar rats were randomly assigned to 11 groups (<i>n</i> = 8 per group), and the study was conducted over 35&#xa0;days. This study investigates the neuroprotective effects of icariin (ICN), a bioactive compound from <i>Epimedium</i>, and tanshinone IIA (TNN), a key component of <i>Salvia miltiorrhiza</i>, in an EtBm-induced MS model. Both compounds modulate critical neuronal pathways, including SIRT-1, Nrf2, and HO-1, and exhibit neuroprotective properties. ICN (15 and 30&#xa0;mg/kg) and TNN (30 and 60&#xa0;mg/kg), alone and in combination (ICN15 + TNN30; ICN30 + TNN30), were orally administered. Fingolimod (FGL0.5) at 0.5&#xa0;mg/kg/day was combined with ICN30 + TNN60. Results demonstrated that ICN and TNN combinations significantly improved locomotor activity, neuromuscular coordination, and cognitive function in MS-induced rats. These combinations reduced inflammatory cytokines, pro-apoptotic markers, and demyelination, while restoring neurotransmitter levels (GABA and glutamate) and antioxidant enzyme activity (SOD and Catalase). The gross and histopathological analyses confirmed reduced demyelination and enhanced myelin repair. The combination of ICN, TNN, and FGL0.5 exhibited more potent neuroprotective effects compared to monotherapy. By modulating key neuronal pathways, ICN and TNN alleviate MS-related symptoms, promote neuroprotection, and enhance remyelination. These findings suggest that ICN and TNN offer a multitarget approach to improve MS-like symptoms in adult Wistar rats, although further investigations are needed to validate their efficacy.</p>

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Multitarget therapeutic potential of icariin and tanshinone IIA via activation of SIRT-1/Nrf2/HO-1 signalling in intracerebral peduncular region ethidium bromide-induced multiple sclerosis-like pathology

  • 期刊论文

  • 发表日期：

    2026年3月13日

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  • Pankaj Kumar Maurya,
  • Sidharth Mehan,
  • Ghanshyam Das Gupta

摘要

Multiple sclerosis (MS) is a chronic immune-mediated disorder of the central nervous system characterised by progressive neuronal demyelination. Its progression is influenced by genetic, environmental, and immunological factors, including abnormal immune responses targeting the myelin sheath. Ethidium bromide (EtBm)-induced demyelination in rat models has provided insights into MS pathology and therapeutic strategies. A total of 88 Wistar rats were randomly assigned to 11 groups (n = 8 per group), and the study was conducted over 35 days. This study investigates the neuroprotective effects of icariin (ICN), a bioactive compound from Epimedium, and tanshinone IIA (TNN), a key component of Salvia miltiorrhiza, in an EtBm-induced MS model. Both compounds modulate critical neuronal pathways, including SIRT-1, Nrf2, and HO-1, and exhibit neuroprotective properties. ICN (15 and 30 mg/kg) and TNN (30 and 60 mg/kg), alone and in combination (ICN15 + TNN30; ICN30 + TNN30), were orally administered. Fingolimod (FGL0.5) at 0.5 mg/kg/day was combined with ICN30 + TNN60. Results demonstrated that ICN and TNN combinations significantly improved locomotor activity, neuromuscular coordination, and cognitive function in MS-induced rats. These combinations reduced inflammatory cytokines, pro-apoptotic markers, and demyelination, while restoring neurotransmitter levels (GABA and glutamate) and antioxidant enzyme activity (SOD and Catalase). The gross and histopathological analyses confirmed reduced demyelination and enhanced myelin repair. The combination of ICN, TNN, and FGL0.5 exhibited more potent neuroprotective effects compared to monotherapy. By modulating key neuronal pathways, ICN and TNN alleviate MS-related symptoms, promote neuroprotection, and enhance remyelination. These findings suggest that ICN and TNN offer a multitarget approach to improve MS-like symptoms in adult Wistar rats, although further investigations are needed to validate their efficacy.