Objective

2

To observe the therapeutic effect and mechanism of the

Tangfukang Formula

on spontaneous diabetes （KKAy） mice.

Methods

2

Thirty-six KKAy mice and six C57BL/6J wild-type mice were selected， with C57BL/6J mice serving as the normal group and receiving a normal diet， while KKAy mice were given a high-fat diet. The 36 KKAy mice were randomly divided into model group， Chinese medicine group， Chinese medicine + inhibitor group， and agonist group according to a random number table， with 9 mice in each group. The Chinese medicine group and Chinese medicine + inhibitor group were administered 3.2 g/（kg·d） of

Tangfukang Formula

by gavage. The normal， model， and agonist groups received an equivalent volume of physiological saline by gavage， once per day for 4 weeks. The agonist group was injected intraperitoneally with 0.5 g/（kg·d） 5-aminoimidazole-4-carboxamide ribonucleotide （AICAR）， an

d the Chinese medicine + inhibitor group was injected with 5 mg/（kg·d） compound C （CC） intraperitoneally. The normal， model， and Chinese medicine groups received an equivalent volume of phosphate buffer solution by intraperitoneal injection， once per day for 4 weeks. Random blood glucose （RBG）， oral glucose tolerance test （OGTT）， plasma adiponectin （APN） and branched-chain amino acids （BCAA）， protein expression levels of AMPKα， p-AMPKα， BCKDH-E1α， and p-BCKDH-E1α in skeletal muscle， as well as histopathological changes in skeletal muscle and pancreatic tissues， were assessed. Safety indicators were also measured.

Result

2

After 2 weeks of intervention， RBG levels in the Chinese medicine group and agonist group were lower than those in the Chinese medicine + inhibitor group （

P

<

0.01）， with no significant difference between the Chinese medicine and agonist groups （

P

>

0.05）. After 4 weeks， RBG levels in the Chinese medicine and agonist groups were significantly reduced compared to those before treatment （

P

<

0.01）， and their RBG levels were lower than those of the model group at all observed time points （

P

<

0.01）. After 4 weeks， plasma APN levels in the model group were lower than in the normal group， while BCAA levels were higher （

P

<

0.05）. Compared with the model group， both the Chinese medicine and agonist groups had higher APN levels and lower BCAA levels （

P

<

0.01）. There was no significant difference in APN and BCAA levels between the Chinese medicine + inhibitor group and the model group （

P

>

0.05）. Histopathological examination showed that in the Chinese medicine and agonist groups， skeletal muscle cells were more orderly with less edema， atrophy， and rupture of muscle fibers， and fewer inflammatory cells. In these groups， the levels of p-AMPKα/AMPKα and p-BCKDH-E1α/BCKDH-E1α in skeletal muscle tissue were significantly higher （

P

<

0.

05）. Compared with the model group， the Chinese medicine and agonist groups showed significantly lower alanine aminotransferase （ALT） levels （

P

<

0.01）， while there was no significant difference in the Chinese medicine + inhibitor group （

P

>

0.05）. The Chinese medicine group also showed significantly lower aspartate aminotransferase （AST）， urea， and creatinine （Crea） levels compared to the model group （

P

<

0.05）， while no significant differences were observed in the agonist and Chinese medicine + inhibitor groups （

P

>

0.05）.

Conclusion

2

Tangfukang Formula

has a clear effect on improving the metabolism of glucose and lipid in KKAy diabetes mice， and has good safety. Its mechanism may be related to APN-AMPK-BCAA signaling pathway.