Warning: Spoilers for Boruto: Naruto Next Generations chapter 75A scene in the early chapters of Boruto suggests that Sakura and even Tsunade could play a big part in defeating the Ōtsutsuki and unlocking the full mystery of Karma.
Like the majority of female ninjas in the manga, Sakura and especially Tsunade have played very insignificant roles, with the former Hokage not even appearing once in the manga. But similar to recent chapters which suggest that Boruto's Sarada and Sumire could play major roles against Eida, so, too, could Sakura and Tsunade.
Readers first learned about their importance when Sarada noticed that the Ōtsutsuki Karma shared a physical resemblance to her mother's Mitotic Regeneration Jutsu forehead mark in Boruto: Naruto Next Generations chapter 35 by creator and supervisor Masashi Kishimoto, artist Mikio Ikemoto and scriptwriter Ukyo Kodachi. Naruto, however, immediately shot down Sarada's comparison since Mitotic Regeneration was a jutsu while Karma's origin was still unknown at the time. But Boruto recently dropped a massive bombshell that all Ōtsutsuki powers are god-tier jutsus known as shinjutsus and that jutsus themselves are a pale imitation of them. Since Mitotic Regeneration and Karma not only share a physical resemblance but are part of the same family of abilities, Karma's secrets could be unlocked upon further study of Mitotic Regeneration.
Boruto's Mitotic Regeneration Could Be Karma's Diluted Form
Sakura isn't the only shinobi with the Mitotic Regeneration mark, however. Tsunade uses the ability to heal wounds, and it is possibly what has kept her looking so young despite her advanced years. How both of them utilize the mark on their forehead also flips one of Karma's primary functions in Boruto, which suggests the Mitotic Generation jujutsu is the diluted form of the Karma shinjutsu. Karma allows the to absorb chaka-based attacks while those who possess Mitotic Regeneration stores and absorbs some of their own chakra every day within their mark for later use. This gradual accumulation of chakra is also similar to how Karma s can perform the same function except with combat experience. The only problem is that the mysterious Amado recently divulged that he has been studying Karma as a means to resurrect his daughter. If he learns that Karma and Mitotic Regeneration are connected somehow, he will likely turn his attention to the latter jutsu and could resort to more inhumane measures of experimentation, especially when considering all of his many attempts of understanding Karma have continuously failed.
Regardless, it's still an exciting prospect that two prominent Naruto characters who have been cast aside in Boruto could return to prominence once more. This is especially the case since the overarching Naruto and Boruto storylines have been unkind to their particular demographic. These developments couldn't come at a more exciting time in the Naruto universe, either. Although Tsunade hasn't had much of a role even in the anime, Sakura's character is currently sharing the spotlight with her husband in the recently adapted light novel series Sasuke's Story. Although Boruto is about the next generation of Naruto, what fans care about is the generation they grew up with, and it looks like that Boruto is finally delivering more of what these fans want and deserve.