A Protection Rune grants you attack immunity (your cities and wilds cannot be attacked by other players).
The best way to use them is right after getting level 10 wilds. You can even flip level 10 wilds, as the rune is up, the wilds cannot be flipped back.
Also, make sure you have enough gold for your heroes, assign your highest level heroes to resource production. If you have food, wood, stone or ore runes, it’s even better.
Ask for resources in your Alliance Chat.
This is it. You will get a nice might boost from using one or two protection runes.
The downside is that you also cannot attack anything, cities or wilds.