Researchers discovered that combining two existing drugs—sinomenine and metformin—may help protect the brain when a stroke occurs in people with type 2 diabetes. Using diabetic rats, scientists found that giving these drugs together before a stroke reduced brain damage and improved recovery better than either drug alone. The protection worked by reducing harmful inflammation and activating the brain’s natural cleanup system. While these results are promising, the research was done in animals, so more testing is needed before doctors can use this combination to treat stroke patients with diabetes.

The Quick Take

  • What they studied: Whether combining sinomenine and metformin could protect the brain from damage during a stroke in animals with type 2 diabetes, and how these drugs work at the cellular level
  • Who participated: Male rats with type 2 diabetes created by feeding them a high-fat diet and giving them a chemical that damages the pancreas. The exact number of rats wasn’t specified in the abstract
  • Key finding: Rats that received both drugs together before a stroke showed better brain function recovery and less brain damage compared to rats receiving either drug alone or no treatment. The combination reduced harmful inflammation and boosted the brain’s natural cleaning system
  • What it means for you: This research suggests a potential new treatment approach for stroke in diabetic patients, but it’s still in early stages. The work was done in animals, so human studies are needed before this combination could be prescribed. If you have diabetes and are concerned about stroke risk, talk to your doctor about proven prevention strategies

The Research Details

Scientists created type 2 diabetes in rats using a high-fat diet combined with a chemical injection. Once the rats developed diabetes, they gave some rats sinomenine, some metformin, some both drugs, and some no treatment for a week. Then they temporarily blocked blood flow to part of the rats’ brains (mimicking a stroke) and allowed blood flow to return. They measured how well the rats recovered using behavior tests and examined brain tissue to see what happened at the cellular level.

To understand how the drugs worked, researchers also tested what happened when they blocked a specific cellular cleanup process called mitophagy. This helped them figure out which mechanism was responsible for the brain protection.

The study measured multiple markers of brain damage including inflammation chemicals, oxidative stress (harmful molecules), and proteins involved in cell death pathways.

This research approach is important because it combines behavioral testing (how well animals function) with detailed molecular analysis (what’s happening inside cells). This combination helps researchers understand not just whether a treatment works, but exactly how it works. Understanding the mechanism is crucial for developing safe and effective human treatments. Testing in diabetic animals is particularly valuable because diabetes changes how the brain responds to stroke, making it more relevant to real patients

This is an animal study published in a peer-reviewed journal, which means other scientists reviewed the work before publication. The researchers measured multiple outcomes and used established scientific methods. However, animal studies don’t always translate to humans—what works in rats may not work the same way in people. The abstract doesn’t specify the exact number of animals used, which makes it harder to assess statistical power. The study was well-designed with appropriate controls and multiple measurement methods, but human clinical trials would be needed to confirm these findings are safe and effective for stroke patients

What the Results Show

Rats receiving the combination of sinomenine and metformin showed significantly better neurological function after stroke compared to control groups. This improvement was measured using standardized behavior tests that assess movement, coordination, and neurological reflexes.

At the cellular level, the combination therapy reduced pyroptosis—a type of cell death that causes inflammation. Specifically, the drugs lowered levels of NLRP3, cleaved caspase-1, and gasdermin D, which are proteins that trigger this harmful cell death process. The combination also reduced pro-inflammatory chemicals (IL-1β and IL-18) that cause swelling and damage in the brain.

The drugs activated the PINK-1/Parkin pathway, which is the brain’s natural system for cleaning up damaged mitochondria (the energy-producing parts of cells). This cleanup process, called mitophagy, appears to be a key mechanism protecting the brain. When researchers blocked this cleanup system with a drug called Mdv-1, the protective effects of the combination therapy disappeared, proving that mitophagy was essential for the benefits.

The combination therapy also improved the brain’s antioxidant defenses by increasing levels of protective enzymes (superoxide dismutase and glutathione peroxidase) while reducing harmful oxidative stress markers (malondialdehyde). This suggests the drugs help the brain defend itself against oxidative damage, which is a major cause of stroke injury. Neither drug alone produced effects as strong as the combination, indicating that sinomenine and metformin work synergistically—together they’re more powerful than either one separately

This research builds on existing knowledge that metformin has some protective effects in the brain and that sinomenine (a compound from a traditional Chinese plant) has anti-inflammatory properties. The novel finding is that combining these two drugs produces stronger protection than either alone, and that this protection specifically works through the mitophagy pathway. Previous research has suggested that blocking pyroptosis and enhancing mitophagy are promising strategies for stroke protection, but this is one of the first studies showing that this combination of drugs can achieve both effects simultaneously in diabetic animals

This study was conducted entirely in animals, so results may not translate directly to humans. The abstract doesn’t specify how many rats were used, making it difficult to assess whether the sample size was adequate. The study only tested male rats, so it’s unclear whether the results would be the same in females. The research used a specific type of stroke model (temporary blockage of one artery), so results might differ with other types of stroke. The drugs were given before the stroke occurred, which is different from real-world scenarios where stroke treatment usually begins after the stroke happens. Finally, this is a single study, so the findings need to be confirmed by other research groups before drawing firm conclusions

The Bottom Line

Based on this animal research, the combination of sinomenine and metformin appears promising for stroke protection in diabetic patients, but it’s too early to recommend it for clinical use. Current evidence level: Preliminary animal research. If you have type 2 diabetes, focus on proven stroke prevention strategies: controlling blood sugar, managing blood pressure, taking prescribed medications, exercising regularly, eating a healthy diet, and not smoking. Talk to your doctor about your individual stroke risk and the best prevention approach for you

This research is most relevant to people with type 2 diabetes who are concerned about stroke risk, as well as neurologists and diabetes specialists researching new treatments. It may eventually be relevant to stroke patients and their families, but only after human clinical trials are completed. People without diabetes should not assume these findings apply to them, as diabetes significantly changes how the brain responds to stroke. This research is not yet ready to guide individual patient treatment decisions

In this animal study, the drugs were given for 7 days before the stroke, and benefits were measured within 24 hours after the stroke. If this approach moves to human trials, it would likely take several years to determine the optimal dosing, timing, and safety profile. Even if human trials are successful, it would typically take 5-10 years before a new combination therapy could become available as a standard treatment

Want to Apply This Research?

  • Track stroke risk factors daily: blood sugar readings (if diabetic), blood pressure, exercise minutes, and medication adherence. Create a weekly summary to share with your healthcare provider
  • Set reminders to take diabetes medications consistently, log daily blood pressure readings, and track 30 minutes of moderate activity most days. These proven strategies reduce stroke risk while researchers continue studying new treatments
  • Establish a baseline of your current stroke risk factors (blood sugar control, blood pressure, cholesterol, weight). Monitor these monthly and review trends with your doctor quarterly. As new research develops, discuss with your healthcare provider whether emerging treatments might be appropriate for you

This research was conducted in animals and has not been tested in humans. The findings are preliminary and should not be used to guide personal medical decisions. Do not start, stop, or change any medications without consulting your healthcare provider. If you have type 2 diabetes or are concerned about stroke risk, work with your doctor to develop a personalized prevention plan based on current evidence-based treatments. In case of stroke symptoms (sudden weakness, numbness, difficulty speaking, or vision changes), call emergency services immediately.