なさい is technically an honorific form because it's originally a slurred imperative form of なさる. However, this does not mean you can use it respectfully to someone of higher status in modern Japanese conversation. The respectful sense has been largely lost over time, and something like 食べなさい or 行きなさい is now basically a command used by a parent or teacher to young children. 食べろ is too strong and is rarely used in real life conversation. Apart from this, 食べなさい is practically the strongest and most dignified command a child will hear on a daily basis. For example, on elementary or middle school exams, you might find instructions like 文章を読んで問題に答えなさい.
When it's used with お/ご, it's a bit different. お食べなさい does sound politer and more respectful than 食べなさい, but this form is fairly uncommon today. Perhaps you would see お + なさい mainly in fairy tales, fantasy works, and novels written more than 100 years ago. In such settings, お + なさい is basically a polite and courteous request/invitation, and occasionally someone of a little lower status may use it as a polite request. You might see お + なされ more often, which is an old form of お + なさい. Anyway, unless you intentionally want to sound old and pompous, you should not use these forms in modern conversation.
As exceptions, お休みなさい ("Good night") and お帰りなさい ("Welcome back") are fixed greetings that are almost always safe regardless of the social status. It's perfectly natural and safe to say these to your boss in your office.
