Natural occurring inhibitors of cyclin-dependent protein kinase 5 (Cdk5), isolated from the root of Rhodiola rosea are structurally different from the known Cdk inhibitors. They show selectivity among different Cdks and have efficacy to inhibit Cdk via a mixed-type of inhibition, which should lead to less toxicity and side-effects. They are useful in preventing and treating diseases and disorders associated with aberrant Cdk5 activities, such as acute and/or chronic pain, neuropathic pain, diabetes mellitus, cancer, neurodegenerative diseases and neuropathological disorders.