Table 1.

Recent pharmacological studies complemented with NMR approaches for evaluating the efficacy/safety of new or existing drugs.

Tested Substance	Evaluated Effect	NMR Experiments Used in the Study	Ref.
Isoniazid (INH)	INH induces oxidative stress, disturbs energy metabolism, and causes disorders in neurotransmission and neuromodulation processes in Sprague Dawley rats.	1H-NMR CPMG 1H,1H-TOCSY 1H,13C-HSQC	[178]
Naproxen	Naproxen induces a disturbance in energy and choline metabolism, and promotes catabolism of tryptophan in Sprague Dawley rats.	1H-NOESYPRESAT-1D	[179]
Cisplatin (CP)	Identification of six serum (alanine, betaine, glucose, glutamine, lactate, and leucine) and eight urinary (alanine, acetate, citrate, glucose, glycine, guanidinoacetate, hippurate, and lactate) metabolites that can be used as biomarkers for cisplatin nephrotoxicity.	1H-NMR	[180]
Shell of Herpetospermum caudigerum Wall (SHCW)	A high dosage of SHCW causes the disturbance of energy and amino acid metabolism and induces oxidative stress in Sprague-Dawley rats.	1H-NMR CPMG 1H,13C-HSQC 1H,13C-TOCSY	[86]
Ampicillin, Maculatin 1.1	Both antibiotics cause destabilization of membrane integrity and increase breakdown of nucleic acids in E. coli.	1H-31P CP	[94]
Emodin	Emodin can affect the immune response and interrupt energy metabolism (citric acid cycle) along with glutathione synthesis, which can lead to oxidative stress.	1H-NMR CPMG 1H,1H-COSY 1H,13C-HMBC 1H,13C-HSQC	[65]
“RenqingMangjue” pill (RMP)	RMP can disturb the citric acid cycle in cells, and decreases levels of glutamate, glutamine and BCAAs in the plasma of Wistar rats.	1H-NMR CPMG 1H,1H-COSY 1H,13C-HSQC 1H-13C HMBC	[66]
Ptac2S	Ptac2S limits cancer cell (Skov-3) proliferation by reducing the efficiency of the citric acid cycle and induces changes in cell membranes in a shorter period of time (6h) compared to cisplatin (24h). Additionally, Ptac2S may inhibit lactate dehydrogenase.	1H-NMR CPMG 1H,1H-COSY 1H,13C-HSQC 1H,13C-HMBC	[145]
Gemcitabine-carboplatin (GC)	Identification of two biomarkers (formate and acetate) that can predict a positive response in MBC (metastatic breast cancer) patients treated with GC chemotherapy.	1H-NMR CPMG 1H JRES 1H,1H-COSY 1H,1H-TOCSY 1H,13C-HSQC 1H,13C-HMBC	[137]
Doxorubicin (DOX)/dexrazoxane (DEX)	DOX decreases ATP production and induces oxidative stress in H9C2 cells. DEX counteracts those changes, having a cardioprotective effect on H9C2 cell lines.	1H-NOESYPRESAT-1D	[67]
Curcumin	Curcumin shows antihyperlipidemic effects on C57BL/6Slac mice by partially restoring metabolic defects induced by a high-fat diet. Affected metabolic pathways include the citric acid cycle, glycolysis and gluconeogenesis, ketogenesis of BCAA, synthesis of ketone bodies and cholesterol, and choline and fatty acid metabolism.	1H-NOESYPRESAT-1D 1H-1H TOCSY 1H,13C-HSQC	[136]
Formosanin C (FC)	Formosanin C shows the ability to inhibit synthesis and methylation of DNA as well as reducing the activity of the citric acid cycle and energy metabolism in the mitochondria of HepG2 cells.	1H-NMR	[181]
Melamine	Melamine disrupts metabolism of glucose, nitrogen, and protein in the liver of Wistar rat.	1H-NMR CPMG	[182]
Aristolochic acid (AA)	Aristolochic acid causes renal lesions and a disorder in tubular reabsorption in Wistar rats.	1H-NMR	[68]
Rituximab	Evaluating response outcome for patients with rheumatoid arthritis, treated with rituximab. Identification of metabolites changes between responders and non-responders such as succinate, taurine, lactate, pyruvate and aspartate.	1H-NMR	[183]
Levetiracetam, Lamotrigine, Topiramate	No distinction between metabolite profiles of serum from patients treated with levetiracetam, lamotrigine and topiramate. Could not evaluate response of initial treatment of epilepsy.	1H-NOESYPRESAT-1D	[184]
Hexacationic Ruthenium Metallaprism	Metallaprism mainly affects lipid metabolism in A2780 (human ovarian cancer) and HEK-293 (human embryonic kidney) cells, and increases GSH levels in all cell lines. In A2780cisR (cisplatin resistant A2780) cells, lipid biogenesis and glycosylation are affected by treatment with metallaprism.	HR-MAS: a)1D -1H NOESY -1H CPMG b)2D -1H,1H-TOCSY -1H J-resolved	[138]
Centella asiatica extract	Extract from Centella asiatica promotes glycolysis, boosts the citric acid cycle and decreases gluconeogenesis and lipid metabolism in T2DM Sprague–Dawley rats.	1H-NMR CPMG	[185]
VR24, VR27 (1,3,4-thiadiazoles)	VR24 and VR27 improve glycerol metabolism, decrease betaine levels, and normalize the altered level of myoinositol in serum of DMH-induced CRC (colorectal cancer) Wistar rats.	1H-NMR CPMG	[186]
Xiaoyaosan	Xiaoyaosan regulates energy metabolism, can play an important role in the regulation of the nervous system, and might restore the balance in gut microbiota of depressed patients.	1H-NMR CPMG 1H,1H-COSY 1H,13C-HMQC	[187]
Sini decoction (SND)	SND may restore balance in myocardial energy metabolism, and regulate the citric acid cycle and amino acid metabolism. Identification of 10 biomarkers showing potential efficiency of SND administration in Sprague-Dawley rats.	1H-NMR	[188]
Fu Fang Jin Jing Oral Liquid (FJJOL) with Herba Rhodiol	FJJOL regulates energy metabolism of brain tissue, can affect the function of neurons abundant in GABA and glycine receptors, and may help to maintain the membrane integrity of the cells in Kunming-strain mice exposed to hypobaric hypoxia.	1H-NOESYPRESAT-1D 1H,1H-gCOSY 1H,1H-TOCSY	[87]
Acyclovir, Pyrazinamide, Isoniazid, Sulfamethoxazole	Evaluating the efficacy (determined by the concentration of a drug able to reach the therapeutic site) of four drugs in cerebrospinal fluid of tuberculous meningitis patients.	1H-NOESYPRESAT-1D 1H,1H-COSY	[189]
Genipin	Genipin can recover energy metabolism to normal levels, and regulate methylamine and amino acid metabolisms of diabetic Sprague Dawley rats.	1H-NOESY-1D	[190]
Adriamycin (ADR)	Identification of seven biomarkers: trimethylamine oxide (TMAO), taurine, trimethylamine (TMA), hippurate, trigonelline, citrate and 2-oxoglutarate that can predict tumor’s (gastric adenocarcinoma) response to ADR treatment in BALB/c-nu/nu mice.	1H-NOESYPRESAT-1D	[191]
Danggui/European Danggui	Comparison between Danggui and European Danggui showed that Danggui has a different chemical composition and provides a better enriching effect on blood than European Danggui. Identification of 18 metabolites affected by Danggui treatment.	1H-NMR CPMG 1H-NOESYPRESAT-1D 1H,1H-COSY 1H,13C-HSQC	[88]
Erythromycin	Erythromycin decreases citric acid cycle activity, enhances fatty acid oxidation, causes dysfunction in amino acid metabolism, and creates oxidative stress in livers of Wistar rats.	1H-NMR CPMG 1H-NMR BPPLED	[192]
Fuzi/Gancao	Fuzi causes a shift in energy metabolism (from aerobic respiration to anaerobic), induces membrane toxicity, and disrupts the balance of gut microbiota of Wistar rats. Administrating Fuzi with Gancao diminishes the toxic effects of Fuzi.	1H-NOESY-1D	[193]
Kijitsu, Tohi, Chimpi, Kippi, Seihi	1H-NMR spectra enabled the identification of three compounds (naringin, sucrose, and β-glucose), and 13C-NMR enabled the identification of eight compounds (naringin, neohesperidin, ɑ- and β-glucose, sucrose, limonene, narirutin, and synephrine).	1H-NMR 13C-NMR	[112]