When i say "What's up?"? what's the main means this sentence?
It's used both as a salutation, along the lines of "how are things?", "how are you?", etc. and as a specific enquiry if someone appears to be disturbed or unhappy about something. So, I might meet a friend in the street and ask "hey, what's up?" to which the reply might be "nothing much." Or I could see a child crying and ask "what's up, little one?"