Here's another vote for the .22 Bersa / Firestorm. I think it is hard to beat for the price. Mine, however, has doubled in cost because a female friend asked to "borrow" it and I'll likely have to buy another. Her idea of "borrow" seems not to have a time limit.
I also really like my Walther P22. I did not find learning how to use the safety to be difficult, but I do think it is superfluous. It is also sensitive to ammo choices, to I suggest working with several to find one that works with 100% reliability. Mine does not like bare lead bullets, nor low velocity ones. I also bought the longer barrel for it. It looks like a compensator and adds muzzle weight if you want it. It is also fussy about staying in place, so I suggest that if you like it, you Lock Tite it in place. Or, just stick with the short barrel.
The best .22 auto I have, for my uses, is the Sig Trailside Hammerli. I see them selling used for under $300. I have a S&W 41 that cost more than twice as much, but does not deliver more practical accuracy. I've often used the Sig to "hunt" flies and wasps that congregated around some strategically spilled sugary soda. I easily whacked them from 25 - 30 feet, off-hand, open sights. It is less sensitive to ammo choices than the Walther.
I find the slides on all of these to be very easy to operate, but I think your friend may have difficulty disassembling them for cleaning. Offer to help.
It's possible she'll need both hands to release the slide stop, too, but in my opinion wrist strength or pain due to arthritis is not the issue, there.
If she buys it at a friendly local gun shop, they may offer to clean it for her, no charge. I have seen that offered to senior citizen buyers. Wouldn't hurt to ask, but tell her to take it in unloaded.