All you have to do if you are modifying the xml directly is save the file and start a new game. (You might be able to continue an old game, depending on what was changed, but you must start the program after saving the xml changes)
If you are using the excel editor, you have to click "Export" for the xml files themselves to change. You also need to have Macro's allowed. After that, you still need to restart the game for it to register.
Also make sure you are going to the right location. It is usually recommended that for your personal modmod you should modify a copy instead of the original file. If you do this, you should remember to change the target of the shortcut. Otherwise you may still be opening and trying to play the unmodded version.