Agnuside is a major active iridoid glycoside found in Vitex agnus-castus (chaste tree), a medicinal plant traditionally used for various gynecological conditions, including premenstrual syndrome (PMS). PMS Type D (depressive type) is characterized by mood disturbances such as depression and irritability. Several clinical studies and systematic reviews have investigated the efficacy of Vitex agnus-castus extracts in alleviating PMS symptoms, including mood-related complaints. The mechanism is thought to involve dopaminergic activity leading to a reduction in prolactin levels, which may positively influence mood-related symptoms.

While most studies have evaluated whole-plant extracts rather than isolated agnuside, agnuside is consistently identified as a key active compound responsible for the plant's effect on the hypothalamic–pituitary axis. For example, a 2017 review in Phytomedicine and a 2019 Cochrane Review concluded that Vitex agnus-castus extracts can significantly reduce overall PMS symptoms, including depression, compared to placebo, though the studies vary in quality and often include other symptom types. Direct evidence for agnuside alone in PMS Type D is limited, but its role as a marker compound and the central component in standardized extracts lends moderate scientific support. Further, the safety profile of Vitex is generally favorable in short-term use.

In summary, there is moderate scientific evidence (primarily for whole-plant extracts rich in agnuside) to support its use for PMS with depressive symptoms (Type D), but high-quality, agnuside-specific trials are lacking.