In recent years, there has been much interest in interactions between botanicals and drugs, that is, the ability of medicinal "herbs" to influence the pharmacokinetics (absorption, metabolism, or excretion) of pharmaceuticals. This interest was sparked by the rising awareness that the prevalence of herbal supplement use was high in the general population and higher yet in patients with chronic diseases requiring regular intake of a variety of medications. Reports of life-threatening consequences resulting from herb-drug interactions further underscored the urgent need for a better understanding of these interactions.
The metabolism or biotransformation of drugs and many other chemicals and environmental pollutants ultimately results in their excretion and is, therefore, referred to as detoxification. Detoxification is at least a two-step process and is mediated by phase I and phase II enzymes. Phase I reactions are catalyzed by members of the cytochrome P450 system, which are located mainly in the liver, but are also present in gut wall, lung, and kidney. The cytochrome P450 enzymes are monooxygenases, that is, they use oxygen in order to add a reactive group. The metabolite resulting from this activation can be more reactive or toxic than the parent compound and can cause damage unless phase II enzymes further metabolize it. Phase II enzymes catalyze conjugation reactions, that is, they conjugate the metabolites arising from phase I reactions with molecules like glutathione, glucuronic acid, sulfate, or a variety of amino acids. The effect of medicinal botanicals on cytochrome P450 enzymes has been the focus of extensive research. It is, therefore, rather surprising that the interaction of Spirulina (now called Arthrospira) with this large family of enzymes has rarely been investigated.
EFFECTS OF SPIRULINA ON CYTOCHROME P450, CYTOCHROME P450 REDUCTASE, AND GLUTATHIONE TRANSFERASE
In Swiss albino mice, oral administration of Spirulina fusiformis at a dose of 800 mg/kg body weight for 10 days resulted in a significant decrease in hepatic cytochrome P450 content, whereas cytochrome b5 content was not significantly affected.1'2 Cytochrome b5 is a group of electron transport hemoproteins that enhance the efficiency of certain P450 isoforms. In contrast, the activity of the phase II enzyme glutathione S-transferase (GST) was increased in the liver of these mice. However, according to the p value of <0.1, this increase was at best marginally significant in both of these studies, although the actual data in one of them suggest a very marked elevation with little standard deviation.1 GST was not increased in any of the other tissues examined, which included kidney, lung, and intestine.1 Glutathione reductase activity and concentrations of reduced glutathione were not significantly altered.1,2
The same group of researchers obtained somewhat different results in another investigation of phase I and phase II enzymes in the same strain of mice, treated with 250 or 500 mg/kg body weight of S. platensis orally for 15 days.3 The liver of these animals contained similar levels of cytochrome P450 and cytochrome b5 as untreated controls, whereas cytochrome P450 reductase, and b5 reductase activities were significantly up-regulated. GST and DT diaphorase, which is considered a detoxification enzyme, also exhibited significantly higher activity after Spirulina treatment. Interestingly, the lower dose frequently resulted in greater stimulation than the higher dose. In the same study, oral administration of Spirulina to Swiss albino mice significantly reduced tumor incidence and tumor burden after treatment with two different carcinogens. Unfortunately, the effect of Spirulina on detoxifying enzymes was only examined in healthy mice, but not in those exposed to tumor-inducing chemicals. The reasons for these discrepancies are not immediately obvious, but may involve differences in the dosage and duration of Spirulina administration.
Another group of researchers did not observe a significant effect of orally administered S. fusiformis at doses of 250 and 500 mg/kg per day for 5 days on GST activity in liver of mice.4 At the highest dose (1000 mg/kg), however, Spirulina significantly induced GST activity. In the same study, Spirulina was found to dose dependently reverse the inhibition of GST activity seen after treatment with cyclophosphamide or mitomycin-C, with the highest dose resulting in complete normalization. Similarly, Spirulina significantly attenuated the inhibition of GST activity induced by cisplatin and urethane, and again the highest dose essentially normalized the activity of this enzyme.5 Of note, urethane undergoes metabolic activation through cyto-chrome P450, and part of the protective effect of Spirulina could be due to inhibiting this process.
There is also one investigation of the ability of phycocyanin to influence cytochrome P450 enzymes. Phycocyanin is a major protein of Spirulina, making up 15-20% of algal dry weight. It consists of the apoprotein and covalently attached phycocyanobilin chromophores, which are responsible for the blue coloring of these cyanobacteria. Phycocyanin by itself did not significantly affect hepatic cytochrome P450 activity in rats when administered intraperitoneally.6 However, when injected 1 h before treatment with a single dose of a compound known to cause liver toxicity (R-(+)-pulegone or carbon tetrachloride) phycocyanin significantly, but not completely, reversed the depression of cytochrome P450 activity induced by these hepatotoxins. Interestingly, phycocyanin increased the urinary excretion of one of the major R-(+)-pulegone metabolites, a precursor of more toxic intermediates. Since both the metabolite and the more toxic intermediates arise from P450-mediated reactions, this suggests that phycocyanin inhibited specific components of the P450 system, while possibly inducing others and at the same time reversing the inhibition of overall P450 activity associated with R-(+)-pulegone treatment.
Was this article helpful?
Our internal organs, the colon, liver and intestines, help our bodies eliminate toxic and harmful matter from our bloodstreams and tissues. Often, our systems become overloaded with waste. The very air we breathe, and all of its pollutants, build up in our bodies. Today’s over processed foods and environmental pollutants can easily overwhelm our delicate systems and cause toxic matter to build up in our bodies.