An unusual form of resin (tree sap) was found in Shambhala that had flammable properties. At the start of the game, it was used by Nathan Drake as a sort of UV light to reveal ancient markings (usually clues left behind by Marco Polo that reveal the location of Shambhala) and/or blood; however, it is revealed at the end of the game that the resin possesses the ability to grant near invincibility (thought to be immortality by Polo) to those who consume it. Over time, the consumer also undergoes a physical change, which includes their teeth becoming blackened (as shown on Marco Polo's crew in Borneo) and their skin turning to purple (featured prominently on the Guardians in Shambhala). It is also revealed that the Tree of Life and all of its offspring are the origin of the resin.
It is from the fossilised form of this resin (also known as amber) that the Cintamani Stone was formed, and its unique properties created the legend of the Stone, as well as the powerful Guardians that protected it.
Zoran Lazarević, the main antagonist of Uncharted 2: Among Thieves, consumed sap the resin is made from in the final chapter of the game, which healed the burned portions of his body and granted him superhuman strength, making for an extremely difficult boss fight.
Although there is no proof nor evidence of this, resin may have a distinct scent to it, as Nate often identifies resin by holding it up to his nose. How people came into possession of the resin outside of Shambhala is unknown.