5whole body weight, and lead to the recovery of a raised serum insulin level to
the normal one seen in the control. The preliminary analysis on obesity versus
weight loss indicated that the drugs exert weight-reducing roles accompanied with
anti-inflammation and/or antihypoxia. More importantly, we found for the first
time that a low dose of LPS rather than a high dose of LPS may be a trigger of the
systemic, chronic, and low-grade inflammation (Gao et al. unpublished).
In summary, ART exhibits the multifaceted effects on health and disease through
acting on different targets, i.e., hemoproteins. ART can inhibit bacterial NOS (bNOS)
and cellular NOS to suppress NO production, thereby mitigating NO’s protective role
from antibiotics/chemotherapeutics, and exerting anti-infection and antitumor effects.
ART can also inhibit CAT in bacteria to enhance H 2 O 2 production, which potentates
antibiotics’ bactericidal ability. Accordingly, ART possesses an anti-inflammatory
effect by decreasing a competitive binding of NO to hemoglobin/myoglobin and
repressing the metabolic hypoxia. Furthermore, ART is able to mimic CR and NO for
alkylating mitochondrial COX and initiating mitochondrial uncoupling/biogenesis,
leading to compromised telomere shortening and extended lifespan (Fig. 1.1).
Practically, if you always keep a steady-state NO level derived from
eNOS/nNOS by CR or via supplementation with edible NO, you should have
a lower chance to have inflammatory diseases. Similarly, if you use ART to
inhibit bNOS or iNOS, you should live healthier because of enabling antitumor,
anti-infection, and anti-inflammation. Of course, ART is unable to distinguish
eNOS/nNOS from iNOS, so the best way to amplify the beneficial role of ART is
to inhibit inflammation at first, and then use trace-amount ART.
1.2 A Uniform NO Threshold Theory in Disease and Health
Aging and longevity are constantly the interesting topics in exploring life secrets
since ancient civilization. Even through extensive investigations, it remains myste-
rious how aging is switched and whether longevity can come true. Nevertheless, it
Fig. 1.1 The multifaceted
beneficial effects exerted by
ART through specifically
targeting a variety of
hemoproteins. ART
artemisinin; bNOS bacterial
nitric oxide synthase; COX
cytochrome c oxidase; CR
calorie restriction; NO nitric
oxide; NOS nitric oxide
synthase
1.1 A Brief Story About Discovery on the Pleiotropic Use of ART