Pickering emulsion loaded with total flavonoids from Dracocephalum moldavica L. potentially promotes angiogenesis in the ischemic penumbra after cerebral ischemia reperfusion

Tianyi Gao¹Lu Wu¹Yuru Ma¹Weikai Zhai²Lu Zhang³Wei Cong¹Zhiping Cai¹Chengli Cui^1*Liang Li^1*

• ¹Baotou Medical College, Baotou, China
• ²Xinxiang Centaral Hospital, Xinxiang, China
• ³Cangzhou People's Hospital, Cangzhou, China

Ischemic stroke is a major disease threatening human health. Currently, its therapeutic options are extremely limited, and common thrombolytic therapy tends to cause tissue damage. In contrast, Traditional Chinese (Ethnic) Medicine has a centuries-long clinical history in treating ischemic stroke. Dracocephalum moldavica L., a traditional Mongolian herb distributed in China's Inner Mongolia, is one such example. However, traditional processing and administration of Traditional Chinese (Ethnic) Medicine cannot meet modern medical demands. Furthermore, the active components of Dracocephalum moldavica L. are highly degradable in the environment, creating an urgent need to address the challenges of their extraction and delivery. To address these challenges, this study adopted ultrasonic extraction as an alternative to traditional protocols, thereby improving the extraction efficiency of total flavonoids from Dracocephalum moldavica L. (TFDM). Subsequent animal model validation confirmed that TFDM extracted by this method had significant therapeutic effects: enhancing vascular perfusion in the ischemic penumbra after reperfusion, reducing cerebral infarct volume, and promoting neurological function recovery. Mechanistically, TFDM upregulated the expression of VEGF, VEGFR2, and CD34 in the ischemic penumbra of cerebral ischemia-reperfusion injured rats post-injury. Concomitantly, these molecular changes accelerated microvascular regeneration and microcirculation reconstruction in the ischemic penumbra. Beyond extraction, to overcome the delivery limitations of TFDM, we developed a novel Pickering emulsion fabricated from Starch Sodium Octenylsuccinate (SSOS), chitosan (CS), and tannic acid (TA). This formulation effectively ameliorates the inherent drawbacks of TFDM, including its short storage time and low bioavailability. Overall, this study provides robust evidence for TFDM's neuroprotective effects, supporting its potential as a novel therapeutic candidate for stroke prevention and treatment. Notably, TFDM encapsulated in Pickering emulsion is a practical, efficient approach with promising prospects for future stroke therapy.