Benserazide

The prevalence of Parkinson disease is increasing globally. Despite the existence of effective and affordable medicines for Parkinson disease, access to these medicines is limited in the World Health Organization (WHO) African Region. Several factors influence accessibility, including lack of prioritization of Parkinson disease, shortage of a trained health workforce, barriers to health financing and lack of inclusion of medicines in national essential medicines lists. We determined alignment of the most recent national essential medicines lists of 47 countries in the WHO African Region with the 23rd edition of the WHO Model list of essential medicines for Parkinson disease medicines. Overall, of any formulation or strength, 81% (38/47) of countries included levodopa + carbidopa or levodopa + benserazide as a therapeutic alternative on their national lists; and 79% (37/47) included biperiden or trihexyphenidyl as a therapeutic alternative. Inclusion of specific formulations for medicines was lower; for example, 45% (21/47) of countries included levodopa + carbidopa or levodopa + benserazide in a 4:1 ratio. Furthermore, 11% (5/47) of national essential medicines lists included none of the four medicines. While inclusion of medicines for Parkinson disease in national essential medicines lists provides no guarantee of immediate access, it can encourage procurement, prescribing and use, and can help lower costs, raise awareness of and create political will for Parkinson disease treatment. This analysis provides further evidence of the need for action to improve the accessibility of medicines for Parkinson disease in the WHO African Region.

Hexokinase 2 (HK2) is a critical rate-limiting enzyme in glycolysis, significantly linked to cancer metabolism and drug resistance. We hypothesized that targeting HK2 with Benserazide (BenZ), a known HK2 inhibitor, could potentiate the cytotoxicity of cisplatin (DDP) in non-small-cell lung cancer (NSCLC) cells. Our findings demonstrated that combination of DDP and BenZ significantly enhanced anticancer effects in NSCLC cells, either with or without acquired DDP resistance. In particular, BenZ effectively inhibited ATP and lactate productions. ATP supplementation mitigated the cytotoxicity of the combination treatment, which was restored when both the cisplatin efflux transporters, ATP7A and ATP7B, were simultaneously knocked down. Moreover, BenZ suppressed NF-κB activation and downregulated inflammatory gene expressions, including IκB and RELA phosphorylation, TNF-α, BCL-2, and IL-1β. These effects were attributed to inhibition of HK2 by BenZ leading to the suppression of IκBα phosphorylation. It has been shown that combined use of DDP and BenZ significantly inhibited tumor growth in NSCLC cell xenograft mouse models, while BenZ alleviated the DDP-induced nephrotoxicity. Our findings demonstrate that BenZ inhibits the kinase activity of HK2, reduces ATP level and cisplatin efflux, as well as alleviates NF-κB activation. These multifaceted actions enhance the anticancer efficacy of cisplatin in NSCLC cell models, indicating its potential as an effective adjunct therapy.